Chromatin- and Epigenetics Laboratory

Nuclear DNA is compacted into chromatin which represents a complex structure basically built from repeating units, the nucleosomes. These consist of 145 base pairs of DNA wrapped around an octamer of basic proteins, the core histones. The octamer is formed by 2 molecules each of histones H2A, H2B, H3, and H4. At least 2 different domains can be distinguished in core histones, a globular domain involved in histone-histone interactions (containing the histone fold motif) and the flexible N-terminal tails (of H3 and H4) or N-terminal and C-terminal tails (of H2A and H2B). A series of consecutive nucleosomes produces a beads on a string-structure. A further level of compaction is the 30 nm fiber with 6 nucleosomes per turn in a solenoid arrangement. In the past years our traditional picture of eukaryotic chromatin as a static and largely repressive functional state has changed to a more complex view of chromatin as a highly dynamic state that is essential for regulating cellular functions. The dynamic properties of chromatin are mediated by multiprotein complexes with different functions that set marks overlying the stable information of the DNA. The most prominent factors that influence chromatin structure and function are enzymes that modify the histones and chromatin remodeling machines which utilize ATP. Histones have been conserved during evolution. However, they are dynamically changed by posttranslational modifications. These modifications include acetylation, methylation, phosphorylation, ubiquitination, glycosylation, ADP-ribosylation, carbonylation, sumoylation, and biotinylation which all can cause structural and functional rearrangements in chromatin and therefore represent essential elements of the complex epigenetic histone code. To decipher this code which is recognized and interpreted by transcriptional regulators and chromatin remodeling machines is one of the central challenges of chromatin research.

Our laboratory is particularly interested in the biological function of posttranslational histone modifications. We have extensively characterized and purified histone acetyltransferases and deacetylases in lower eukaryotes (Physarum polycephalum, Aspergillus nidulans, Cochliobolus carbonum and plants (Zea mays, Arabidopsis thaliana). Major breakthroughs were the identification and analysis of a novel type of histone deacetylase in maize, a nucleolar phosphoprotein, unrelated to the well-characterized Rpd3-type deacetylases and the finding that limited proteolysis plays a major role in the regulation of the Rpd3 related deacetylase HDA1 of maize. Our research is now focused on the proteolytic processing pathway of ZmHDA1, the characterization and functional analysis of histone deacetylases in mouse cells and Aspergillus nidulans as well as on histone methyltransferases and putative demethylases in mouse cells and filamentous fungi.

We are currently working on

1. - the identification and functional analysis of histone deacetylases, histone methyltransferases and demethylases in filamentous fungi (Aspergillus, Cochliobolus,Neurospora)
   - role of histone deacetylases in host-microbe interactions
   - mechanism of action of histone deacetylase inhibitors (cyclic tetrapeptides, synthetic inhibitors)
2. - histone acetylation/methylation in mouse cells with a focus on nucleolar chromatin
3. - histone acetyltransferases and deacetylases in plants (maize, sprout, Arabidopsis)
4. - functional signisficance of histone and non-histone modifications for cell cycle regulation
5. - histone methylation in mouse cells
6. - chromatin assembly

Research Teams

• Structure & Function of Chromatin: Maize & Mouse
  
• Structure & Function of Chromatin: Filamentous Fungi
• Chromatin Assembly and Remodeling
  

Members

• Thomas Amort, M.Sc., Ph.D. student
• Ingo Bauer M.Sc., Ph.D., Postdoc
• Anastasiya Boltengagen, M.Sc., technician
• Gerald Brosch M.Sc., Ph.D., Associate Prof.
• Birgit Faber, M.Sc., Ph.D. student
• Stefan Grässle M.Sc., Ph.D., Associate Prof.
• Hermann Krabichler technician
• Adele Loidl Ph.D., guest scientist
• Peter Loidl Ph.D., Prof., Chairman of Microbiology
• Alexandra Lusser M.Sc., Ph.D., Associate Prof.
• Paolo Piatti M.Sc., Ph.D., Postdoc
• Gabriele Scheran M.Sc., technician
• Johanna Sebald, M.Sc., Ph.D. student
• Alexandra Wille, M.Sc., Ph.D. student

Publications

1. Gröbner, P. & Loidl, P. (1982) Action of 5-Fluorodeoxyuridine on synchronous nuclear division and thymidylate synthetase activity in Physarum polycephalum. FEBS Lett. 140, 41.
2. Loidl, P. & Gröbner, P. (1982) Acceleration of mitosis induced by mitotic stimulators of Physarum polycephalum. Exp.Cell Res. 137, 469.
3. Loidl, P., Gröbner, P., Csordas, A. & Puschendorf, B. (1982) Cell cycle dependent effects of sodium-n-butyrate in Physarum polycephalum. J.Cell Sci. 58, 303.
4. Gröbner, P. & Loidl, P. (1982) Thymidylate synthetase during synchronous nuclear division cycle and differentiation of Physarum polycephalum. Biochim.Biophys.Acta 697, 83.
5. Loidl, P. & Sachsenmaier, W. (1982) Control of mitotic synchrony in Physarum polycephalum. Phase shifting by fusion of heterophasic plasmodia contradicts a limit cycle oscillator model. Eur.J.Cell Biol. 28, 175.
6. Gröbner, P. & Loidl, P. (1983) Response of the deoxythymidylate-synthesizing enzymes to differentiation processes in Physarum polycephalum. Exp.Cell Res. 144, 385.
7. Loidl, P., Loidl, A., Puschendorf, B. & Gröbner, P. (1983) Lack of correlation between histone H4 acetylation and transcription during the Physarum cell cycle. Nature 305, 446.
8. Gröbner, P.& Loidl, P. (1984) Thymidine kinase. A novel affinity chromatography of the enzyme and its regulation by phosphorylation in Physarum polycephalum. J.Biol.Chem. 259, 8012.
9. Djondjurov, L., Loidl, P., Yancheva, N., Sachsenmaier, W. & Tsanev, R. (1984) Metabolic behaviour of nonhistone chromosomal proteins during differentiation (spherulation) of Physarum polycephalum. Int.J.Biochem. 16, 1395.
10. Loidl, P., Loidl, A., Puschendorf, B. & Gröbner, P. (1984) RNA polymerase activity and template activity of chromatin after butyrate induced hyperacetylation of histones in Physarum. Nucleic Acids Res. 12, 5405.
11. Gröbner, P. & Loidl, P. (1985) ADP-ribosyltransferase in isolated nuclei during the cell cycle of Physarum polycephalum. Biochem.J. 232, 21.
12. Gröbner, P. & Loidl, P. (1985) An immunological approach to enrich a mitotic stimulator and to reveal G₂-phase specific proteins in Physarum polycephalum. J.Cell Biol. 100, 1930.
13. Loidl, P. & Gröbner, P. (1986) Biosynthesis and posttranslational acetylation of histones during spherulation of Physarum polycephalum. Nucleic Acids Res. 14, 3745.
14. Loidl, P. & Gröbner, P. (1987) Histone synthesis during the cell cycle of Physarum polycephalum: Synthesis of different histone species is not under a common regulatory control. J.Biol.Chem. 262, 10195.
15. Golderer, G., Loidl, P. & Gröbner, P. (1987) Histone-acetyltransferase activity during the cell cycle. FEBS Lett. 222, 322.
16. Loidl, P. & Gröbner, P. (1987) Postsynthetic acetylation of core histones during the cell cycle: a general function for the displacement of histones during chromatin rearrangements. Nucleic Acids Res. 15, 8351.
17. Loidl, P. (1988) Towards an understanding of the biological function of histone acetylation. FEBS Lett. 227, 91.
18. Smolarz, E., Gröbner, P. and Loidl, P. (1988) Periodic fluctuations of nuclear high mobility group like proteins during the cell cycle of Physarum polycephalum. Biochemistry 27, 4142.
19. Golderer, G., Schneider, R., Auer, B., Loidl, P. and Gröbner, P. (1988) ADP-ribosylation in isolated nuclei of Physarum polycephalum. Biochem. J. 253, 859-867.
20. Waitz, W. and Loidl, P. (1988) In situ preparation of the nuclear matrix of Physarum polycephalum. Ultrastructural and biochemical analysis of different isolation procedures. J. Cell Sci. 90, 621-628.
21. Pfaller, W., Gstraunthaler, G. and Loidl, P. (1990) Morphology of the differentiation and maturation of LLCPK₁ epithelia. J. Cellular Physiol. 142, 247-254.
22. Waitz, W. and Loidl, P. (1991) Cell cycle dependent association of c-myc protein with the nuclear matrix. Oncogene 6, 29-35.
23. Golderer, G., Loidl, P. and Gröbner, P. (1991) ADP-ribosylation of the nuclear matrix. Eur. J. Cell Biol. 55, 183-186.
24. Greil, R., Fasching, B., Loidl, P. and Huber, H. (1991) Expression of the c-myc protooncogene in multiple myeloma and chronic lymphocytic leukemia: an in situ analysis. Blood 78, 180-191.
25. López-Rodas, G., Georgieva, E., Sendra, R. and Loidl, P. (1991) Histone acetylation in Zea mays I. Activities of histone acetyltransferases and histone deacetylases. J. Biol. Chem. 266, 18745-18750.
26. Georgieva, E., López-Rodas, G., Sendra, R., Gröbner, P. and Loidl, P. (1991) Histone acetylation in Zea mays II. Biological significance of posttranslational histone acetylation during embryo germination. J. Biol. Chem. 266, 18751-18760.
27. Golderer, G., Loidl, P. and Gröbner, P. (1992) ADP-Ribosylation of the nuclear matrix in Physarum polycephalum. Proceedings of the Cell Biol. Int. Rep. 16, 1145-1150.
28. Brosch, G., López-Rodas, G., Golderer, G., Lindner, H., Gröbner, P. and Loidl, P. (1992) Histone acetyltransferases and histone deacetylases of Physarum polycephalum. Cell Biol. Int. Rep. 16, 1103-1109.
29. López-Rodas, G., Brosch, G., Golderer, G., Lindner, H., Gröbner, P. and Loidl, P. (1992) Enzymes involved in the dynamic equilibrium of core histone acetylation of Physarum polycephalum. FEBS Lett. 296, 82-86.
30. López-Rodas, G., Lang, S., Loidl, A., Fasching, B., Greil, R. and Loidl, P. (1992) Nuclear proto-oncogene homologous proteins during the cell cycle of Physarum polycephalum Cell Biol. Int. Rep. 16, 1185-1191.
31. Greil, R., Fasching, B., Weger, A. and Loidl, P. (1992) Investigation of nuclear c-myc oncoprotein expression in human hematopoiesis: suitability of a rapid and reliable semiquantitative evaluation system based on computer-assisted image analysis. Lab.Invest. 66, 251-260.
32. Grabher, A., Eberharter, A., Gstraunthaler, G. and Loidl, P. (1992) Characterization of nuclear matrix proteins of Physarum polycephalum and mammalian cells. Cell Biol. Int. Rep. 16, 1151-1157.
33. Andreeva, M., Markova, D., Loidl, P. and Djondjurov, L. (1992) Intranuclear compartmentalization of transcribed and non-transcribed c-myc sequences in Namalva-S cells. Eur. J. Biochem. 207, 887-894.
34. Loidl, P., Lucchini, R. and Sogo, J.M. (1992) Histone composition and core histone acetylation of transcriptionally active ribosomal chromatin of Physarum polycephalum. Cell Biol. Int. Rep. 16, 1177-1182.
35. Brosch, G., Georgieva, E., López-Rodas, G., Lindner, H. and Loidl, P. (1992) Specificity of Zea mays Histone Deacetylase Is Regulated by Phosphorylation. J. Biol. Chem. 267, 20561-20564.
36. Lang, S., Decristoforo, T. and Loidl, P. (1992) Synthesis and characterization of nuclear matrix proteins during the cell cycle of Physarum polycephalum. Cell Biol. Int. Rep. 16, 1169-1175.
37. Eberharter, A., Grabher, A., Gstraunthaler, G. and Loidl, P. (1993) Biochemical and immunological characterization of the nuclear matrix: a comparison of the lower eucaryot Physarum polycephalum and a mammalian cell line. Eur. J. Biochem. 212, 573-580.
38. López-Rodas, G., Brosch, G., Georgieva, E.I., Sendra, R., Franco, L. and Loidl, P. (1993) Histone deacetylase - a key enzyme for the binding of regulatory proteins to chromatin. FEBS Lett. 317, 175-180.
39. Lang, S. and Loidl, P. (1993) Identification of proteins immunologically related to vertebrate lamins in the nuclear matrix of the myxomycete Physarum polycephalum. Eur. J. Cell Biol. 61, 177-183.
40. Lang, S., Decristoforo, T., Waitz, W. and Loidl, P. (1993) Biochemical and morphological characterization of the nuclear matrix during the synchronous cell cycle of Physarum polycephalum. J. Cell Sci. 105, 1121-1130.
41. Georgieva, E., López-Rodas, G., Hittmair, A., Feichtinger, H., Brosch, G. and Loidl, P. (1994) Maize embryo germination: I. Cell cycle analysis. Planta 192, 118-124.
42. Georgieva, E., López-Rodas, G. and Loidl, P. (1994) Maize embryo germination: II. Proteins related to nuclear proto-oncogene- and tumor suppressor gene products. Planta 192, 125-129.
43. Loidl, P. (1994) Histone acetylation: facts and questions. Chromosoma 103, 441-449.
44. Grabher, A., Brosch, G., Sendra, R., Lechner, T., Eberharter, A., Georgieva, E.I., López- Rodas, G., Franco, L., Dietrich, H. and Loidl, P. (1994) Intracellular location of enzymes involved in core histone acetylation. Biochemistry 33, 14887-14895.
45. Brosch, G., Ransom, R., Lechner, T., Walton, J. and Loidl, P. (1995) Inhibition of maize histone deacetylases by HC toxin, the host-selective toxin of Cochliobolus carbonum. Plant Cell 7, 1941-1950.
46. Loidl, P. and Eberharter, A. (1995) Nuclear matrix and the cell cycle. Int. Rev. Cytol. 162B, 377-403.
47. Lechner, T., Lusser, A., Brosch, G., Eberharter, A., Goralik-Schramel, M. and Loidl, P. (1996) A comparative study of histone deacetylases of plant, fungal and vertebrate cells. Biochim. Biophys. Acta 1296, 181-188.
48. Eberharter, A., Lechner, T., Goralik-Schramel, M. and Loidl, P. (1996) Purification and Characterization of the Cytoplasmic Histone Acetyltransferase B of Maize Embryos. FEBS Lett. 386, 75-81.
49. Loidl, A. and Loidl, P. (1996) Proto-oncogenes and cell cycle regulators in plants and lower eukaryotes. Crit. Rev. Oncogenesis 7, 49-64.
50. Brosch, G., Goralik-Schramel, M. and Loidl, P. (1996) Purification of Histone Deacetylase HD1-A of Germinating Maize Embryos. FEBS Lett. 393, 287-291.
51. Brosch, G., Lusser, A., Goralik-Schramel, M. and Loidl, P. (1996) Purification and Characterization of a High Molecular Weight Histone Deacetylase Complex (HD2) of Maize Embryos. Biochemistry 35, 15907-15914.
52. Lusser, A., Brosch, G., López-Rodas, G. and Loidl, P. (1997) Histone acetyltransferases during the cell cycle and differentiation of Physarum polycephalum. Eur. J. Cell Biol. 74, 102-110.
53. Lusser, A., Brosch, G., Loidl, A., Haas, H. and Loidl, P. (1997) Identification of maize histone deacetylase HD2 as an acidic nucleolar phosphoprotein. Science 277, 88-91.
54. Jung, M., Hoffmann, K., Brosch, G. and Loidl, P. (1997) Analogues of Trichostatin A and Trapoxin B as histone deacetylase inhibitors. Bioorg. Med. Chem. Lett. 7, 1655-1658.
55. Sommer, A., Hilfenhaus, S., Menkel, A., Kremmer, E., Seiser, C., Loidl, P. and Lüscher, B. (1997) Cell growth inhibition by Mad/Max through recruitment of histone deacetylase activity. Curr. Biol. 7, 357-364.
56. Kölle, D., Sarg, B., Lindner, H. and Loidl, P. (1998) Substrate- and sequential site-specificity of cytoplasmic histone acetyltransferases of maize and rat liver. FEBS Lett. 421, 109-114.
57. Dangl, M., Lusser, A., Brosch, G., Loidl, A., Haas, H. and Loidl, P. (1998) Second Family of Histone Deacetylases. Science 280, 1167.
58. Kölle, D., Brosch, G., Lechner, T., Lusser, A. and Loidl, P. (1998) Biochemical Methods for Analysis of Histone Deacetylases. Methods 15, 323-331.
59. Bauer, A., Mikulits, W., Lagger, G., Stengl, G., Brosch, G. and Beug, H. (1998). The thyroid hormone receptor functions as a ligand-operated developmental switch between proliferation and differentiation of erythroid progenitors. EMBO J. 17, 4291-4303.
60. Hoffmann, K., Brosch, G., Loidl, P. and Jung, M. (1999) A Non-Isotopic Assay for Histone Deacetylase Activity. Nucl. Acids Res. 27, 2057-2058.
61. Kölle, D., Brosch, G., Lechner, T., Pipal, A., Helliger, W., Taplick, T. and Loidl, P. (1999) Different types of maize histone deacetylases are distinguished by a highly complex substrate- and site-specificity. Biochemistry 38, 6769-6773.
62. Lusser, A., Eberharter, A., Loidl, A., Goralik-Schramel, M., Horngacher, M., Haas, H. and Loidl, P. (1999) Analysis of the Histone Acetyltransferase B Complex of Maize Embryos. Nucl. Acids Res. 27, 4427-4435.
63. Jung, M., Brosch, G., Kölle, D., Scherf, H., Gerhäuser, C. and Loidl, P. (1999) Amide analogues of Trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation. J. Med. Chem. 42, 4669-4679.
64. Doetzlhofer, A., Rotheneder, H., Lagger, G., Koranda, M., Kurtev, V., Brosch, G., Wintersberger, E. and Seiser, C. (1999) Histone deacetylase 1 can repress transcription by binding to Sp1. Mol. Cell. Biol., 19, 5504-5511.
65. Lechner, T., Lusser, A., Pipal, A., Brosch, G., Loidl, A., Goralik-Schramel, M., Sendra, R., Wegener, S., Walton, J. and Loidl, P. (2000) Rpd 3 type histone deacetylases in maize embryos. Biochemistry 39, 1683-1692.
66. Graessle, S., Dangl, M., Haas, H., Mair, K., Trojer, P., Brandtner, E.-M., Walton, J., Loidl, P. and Brosch, G. (2000) Characterization of two putative histone deacetylase genes from Aspergillus nidulans. Biochim. Biophys. Acta 1492, 120-126.
67. Hoffmann, K., Brosch, G., Loidl, P. and Jung, M. (2000) First non-radioactive assay for in vitro screening of histone deacetylase inhibitors. Pharmazie 55, 601-606.
68. Lechner, T., Carrozza, M.J., Yu, Y., Grant, P.A., Eberharter, A., Vannier, D., Brosch, G., Stillmann, D.J., Shore, D. and Workman, J.L. (2000). Sds3 (Suppressor of Defective Silencing 3) is an integral component of the yeast Sin3/Rpd3 HDAC complex and is required for histone deacetylase activity. J. Biol. Chem. 275, 40961-40969.
69. Dangl, M., Brosch, G., Haas, H., Loidl, P. and Lusser, A. (2001) Comparative analysis of HD2 type histone deacetylases in higher plants. Planta 213, 280-285.
70. Lusser, A., Kölle, D. and Loidl, P. (2001) Histone acetylation: Lessons from the plant kingdom. Trends Plant Sci. 6, 59-65.
71. Loidl, P. (2001) Introduction: assembly, remodeling and modification of chromatin. Cell. Mol. Life Sci. 58, 663-664.
72. Graessle, S., Loidl, P. and Brosch, G. (2001) Histone acetylation: plants and fungi as model systems for the investigation of histone deacetylases. Cell. Mol. Life Sci. 58, 704-720.
73. Massa, S., Mai, A., Sbardella, G., Esposito, M., Ragno, R., Loidl, P. and Brosch, G. (2001) 3-(4-Aroyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides, a new class of synthetic histone deacetylase inhibitors. J. Med. Chem. 44, 2069-2072.
74. Brosch, G., Baidyaroy, D., Ahn, J., Graessle, S., Wegener, S., Tonukari, N.J., Caballero, O., Loidl, P. and Walton, J.D. (2001). A gene related to yeast HOS2 histone deacetylase affects extracellular depolymerase expression and virulence in a plant pathogenic fungus. Plant Cell 13, 1609-1624.
75. Wagner, M., Brosch, G., Zwerschke, W., Seto, E., Loidl, P. and Jansen-Dürr, P., (2001). Histone deacetylases in replicative senescence: Evidence for a senescence-specific form of HDAC-2. FEBS Lett. 499,101-106
76. Brosch, G., Dangl, M., Graessle, S., Loidl, A., Trojer, P., Brandtner, E.M., Mair, K., Walton, J.D., Baidyaroy, D. and Loidl, P. (2001). An inhibitor-resistant histone deacetylase in the plant pathogenic fungus Cochliobolus carbonum. Biochemistry 40, 12845-12863.
77. Taplick, J., Kurtev, V., Kroboth, K., Posch, M., Lechner, T. and Seiser, C. (2001). Homo-Oligomerisation and Nuclear Localisation of Mouse Histone Deacetylase. J. Mol. Biol. 308, 27-38.
78. Chiocca, S., Kurtev, V., Colombo, R., Boggio, R., Sciurpi, M.T., Brosch, G., Seiser, C., Draetta, G.F. and Cotten, M. (2002). Histone deacetylase 1 inactivation by an adenovirus early gene product. Curr. Biol. 12, 594-598.
79. Mai, A., Massa, S., Ragno, R., Esposito, M., Sbardella, G., Nocca, G., Scatena, R., Jesacher, F., Loidl, P. and Brosch, G. (2002). Binding Mode Analysis of 3-(4-Benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide: A New Synthetic Histone Deacetylase Inhibitor Inducing Histone Hyperacetylation, Growth Inhibition, and Terminal Cell Differentiation. J. Med. Chem. 45, 1778-1784.
80. Wittich, S., Scherf, H., Xie, C., Brosch, G., Loidl, P., Gerhäuser, C. and Jung, M. (2002). Structure-activity relationships on phenylalanine containing inhibitors of histone deacetylase - In-vitro enzyme inhibition, induction of differentiation and inhibition of proliferation in Friend leukemic cells. J. Med. Chem. 45, 3296-3309.
81. Vietor, I., Vadivelu, S.K., Wick, N., Hoffman, R., Cotten, M., Seiser, C., Fialka, Î., Wunderlich, W., Haase, A., Korinkova, G., Brosch, G. and Huber, L.A. (2002). TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells. The EMBO Journal 21, 4621-4631.
82. Brandtner, E.M., Lechner, T., Loidl, P. and Lusser, A. (2002). Molecular identification of PpHDAC1, the first histone deacetylase from the slime mold physarum polycephalum. Cell Biol. Int. 26, 783-789.
83. Lusser, A. (2002). Acetylated, methylated, remodeled: chromatin states for gene regulation. Curr. Opin.Plant Biol., 5: 437-443.
84. Baidyaroy, D., Brosch, G., Graessle, S., Trojer, P. and Walton, J.D. (2002). Characterization of inhibitor-resistant histone deacetylase activity in plant-pathogenic fungi. Eukaryotic Cell 1, 538-547.
85. Mai, A., Massa, S., Ragno, R., Cerbara, I., Jesacher, F., Loidl, P. and Brosch, G. (2003). 3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-alkylamides as a New Class of Synthetic Histone Deacetylase Inhibitors. 1. Design, Synthesis, Biological Evaluation, and Binding Mode Studies Performed Through Three Different Docking Procedures. J. Med. Chem. 46, 512-24.
86. Rossi, V., Locatelli, S., Lanzanova, C., Boniotti, B., Varotto, S., Pipal, A., Goralik-Schramel, M., Lusser, A., Glatz, C., Gutierrez, C. and Motto, M. (2003). A maize histone deacetylase and retinoblastoma-related protein physically interact and cooperate in repressing gene transcription. Plant. Mol. Biol. 51, 401-413.
87. Trojer, P., Brandtner, E.M., Brosch, G., Loidl, P., Galehr, J., Linzmaier, R., Haas, H., Mair, K., Tribus, M. and Graessle, S. (2003). Histone deacetylases in fungi: novel members, new facts. Nucl. Acids Res. 31, 3971-3981.
88. Pipal, A., Goralik-Schramel, M., Lusser, A., Lanzanova, C., Sarg, B., Loidl, A., Lindner, H., Rossi, V. and Loidl, P. (2003). Regulation and Processing of Maize Histone Deacetylase HDA1 by Limited Proteolysis. Plant Cell 15, 1904-1917.
89. Varotto, S., Locatelli, S., Canova, S., Pipal, A., Motto, M. and Rossi, V. (2003). Expression profile and cellular localization of maize Rpd3-type histone deacetylases during plant development. Plant Physiol. 133, 606-617.
90. Mai, A., Massa, S., Pezzi, R., Rotili, D., Loidl, P. and Brosch, G. (2003). Discovery of (aryloxopropenyl)pyrrolyl-hydroxyamides as selective inhibitors of class IIa histone deacetylase homologue HD1-A. J. Med. Chem. 46, 4826-4829.
91. Lusser, A., and Kadonaga, J.T. (2003). Chromatin remodeling by ATP-dependent molecular machines. BioEssays 25, 1192-1200.
92. Mai, A., Massa, S., Cerbara, I., Valente, S., Ragno, R., Bottoni, P., Scatena, R., Loidl, P. and Brosch, G. (2004). 3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 2. Effect of pyrrole-C2 and/or -C4 substitutions on biological activity. J. Med. Chem. 47, 1098-1109.
93. Loidl, P. (2004). A plant dialect of the histone language. Trends Plant Sci. 9, 84-90.
94. Ragno, R., Mai, A., Massa, S., Cerbara, I., Valente, S., Bottoni, P., Scatena, R., Jesacher, F., Loidl, P. and Brosch, G. (2004). 3-(4-Aroyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides as a New Class of Synthetic Histone Deacetylase Inhibitors. 3. Discovery of Novel Lead Compounds Through Structure-Based Drug Design and Docking Studies. J. Med. Chem. 47, 1351-1359.
95. Alexiadis, V., Lusser, A., Kadonaga, J.T.(2004). A conserved N-terminal motif in Rad54 is important for chromatin remodeling and homologous strand pairing. J. Biol. Chem. 279, 27824-27829.
96. Trojer, P., Dangl, M., Bauer, I., Graessle, S., Loidl, P. & Brosch, G. (2004). Histone methyltransferases in Aspergillus nidulans: evidence for a novel enzyme with a unique substrate specificity. Biochemistry 43, 10834-10843.
97. Lusser, A. & Kadonaga, J.T. (2004). Strategies for the reconstitution of chromatin. Nat. Methods 1, 19-26.
98. Hildmann, C., Ninkovic, M., Dietrich, R., Wegener, D., Riester, D., Zimmermann, T., Birch, O. M., Bernegger, C., Loidl, P. & Schwienhorst, A. (2004) A new amidohydrolase from Bordetella or Alcaligenes strain FB188 with similarities to histone deacetylases. J. Bacteriol. 186, 2328-2339.
99. Lusser, A., Urwin, D.L. & Kadonaga, J.T. (2004). Distinct Activities of CHD1 and ACF in the ATP-dependent of Chromatin. Nat. Struct. Mol. Biol. 12, 160-166.
100. Marx, F., Salvenmoser, W., Kaiserer, L., Graessle, S., Weiler-Gorz, R., Zadra, I. & Oberparleiter, C. (2005). Proper folding of the antifungal protein PAF is required for optimal activity. Res. Microbiol. 156, 35-46.
101. Vance, K.W., Carreira, S., Brosch, G. & Goding, C.R. (2005). Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas. Cancer Res. 65, 2260-2268.
102. Rottmann, S., Menkel, A.R., Bouchard, C., Mertsching, J., Loidl, P., Kremmer, E., Eilers, M., Lüscher-Firzlaff, J., Lilischkis, R. & Lüscher, B. (2005). Mad1 Function in Cell Proliferation and Transcriptional Repression is Antagonized by Cyclin E/CDK2. J. Biol. Chem., 280, 15489-15492.
103. Mai, A., Massa, S., Pezzi, R., Simeoni, S., Rotili, D., Nebbioso, A., Scognamiglio, A., Altucci, L., Loidl, P. & Brosch, G. (2005). Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides. J. Med. Chem. 48, 3344-3353.
104. Tribus, M., Galehr, J., Trojer, P., Brosch, G., Loidl, P., Marx, F., Haas, H. & Graessle, S. (2005). HdaA, a Major Class 2 Histone Deacetylase of Aspergillus nidulans Affects Growth Under Conditions of Oxidative Stress. Eukaryot. Cell 4, 1736-1745.
105. Vietor, I., Kurzbauer, R., Brosch, G. & Huber, L.A. (2005). TIS7 regulation of the beta-catenin / TCF-4 target gene OPN is histone deacetylase dependent J. Biol. Chem. 280, 39795-39801.
106. Mai, A., Massa, S., Pezzi, R., Valente, S., Loidl, P. & Brosch, G. (2005). Synthesis and Biological Evaluation of 2-, 3-, and 4-Acylaminocinnamyl-N-hydroxyamides as Novel Synthetic HDAC Inhibitors. Med. Chem. 1, 245-254.
107. Mai, A., Massa, S., Rotili, D., Pezzi, R., Bottoni, P., Scatena, R., Meraner, J. & Brosch, G. (2005). Exploring the connection unit in the HDAC inhibitor pharmacophore model: Novel uracil-based hydroxamates. Bioorg. Med. Chem. Lett. 15, 4656-4661.
108. Causevic, A., Gentil, M.-V., Delaunay, A., Abu El-Soud, W., Garcia, Z., Pannetier, C., Brignolas, F., Hagege, D. & Maury, S. (2006). Relationship between DNA methylation and histone acetylation levels, cell redox and cell differentiation states in sugarbeet lines Planta 224, 812-827.
109. Meraner, J., Lechner, M., Loidl, A., Goralik-Schramel, M., Voit, R., Grummt, I. & Loidl, P. (2006). Acetylation of UBF changes during the cell cycle and regulates the interaction of UBF with RNA polymerase I Nucl. Acids Res. 34, 1798-1806.
110. Mai, A., Massa, S., Valente, S., Simeoni, S., Ragno, R., Bottoni, P., Scatena, R. & Brosch, G. (2006). Aroyl-pyrrolyl hydroxyamides: Influence of pyrrole C4-phenylacetyl substitution on histone deacetylase inhibition Chem.Med.Chem. 1, 225-237.
111. Hildmann, C., Wegener, D., Riester, D., Hempel, R., Schober, A., Meraner, J., Giurato, L., Guccione, S., Nielsen, TK., Ficner, R. & Schwienhorst, A. (2006). Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases. J. Biotechnol. 124, 258-270.
112. Mai, A., Massa, S., Rotili, D., Simeoni, S., Ragno, R., Botta, G., Nebbioso, A., Miceli, M., Altucci, L., & Brosch, G. (2006). Synthesis and biological properties of novel, uracil-containing histone deacetylase inhibitors. J. Med. Chem. 49, 6046-6056
113. Mai, A., Rotili, D., Massa, S., Brosch, G., Simonetti, G., Passariello, C., Palamara, A. T. (2007). Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans. Bioorg. Med. Chem. Lett. 17, 1221-1225.
114. Furchert, S.E., Lanvers-Kaminsky, C., Juergens, H., Jung, M., Loidl, A. & Fruehwald, M.C. (2007). Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumours of the nervous system of childhood. Int. J. Cancer 120, 1787-1794.
115. Ragno, R., Simeoni, S., Castellano, S., Vicidomini, C., Mai, A., Caroli, A., Tramontano, A., Bonaccini, C., Trojer, P., Bauer, I., Brosch, G. and Sbardella, G. (2007). Small Molecule Inhibitors of Histone Arginine Methyltransferases: Homology Modeling, Molecular Docking, Binding Mode Analysis and Biological Evaluations. J. Med. Chem. 50, 1241-1253.
116. Mai, A., Valente, S., Cheng, D., Perrone, A., Ragno, R., Simeoni, S., Sbardella, G., Brosch, G., Nebbioso, A., Conte, M., Altucci, L., and Bedford, M.T. (2007). Synthesis and Biological Validation of Novel Synthetic Histone/Protein Methyltransferase Inhibitors. Chem. Med. Chem. 2, 987-991.
117. Spannhoff, A., Heinke, R., Bauer, I., Trojer, P., Metzger, E., Gust, R., Schuele, R., Brosch, G., Sippl, W. and Jung, M. (2007). Target-based approach to inhibitors of histone arginine methyltransferases. J. Med. Chem. 50, 2319-2325.
118. Shwab, E.K., Bok, JW., Tribus, M., Galehr, J., Graessle, S. and Keller, N. (2007). Histone deacetylase activity regulates chemical diversity in Aspergillus nidulans. Euk. Cell 9, 1656-1664.
119. Mai, A., Jelicic, K., Rotili, D., Di Noia, A., Alfani, E., Valente, S., Altucci, L., Nebbioso, A., Massa, S., Galanello, R., Brosch, G., Migliaccio, A.R. & Migliaccio, G. (2007). Identification of two New Synthetic Histone Deacetylase Inhibitors that Modulate Globin Gene Expression in Erythroid Cells from Normal Donors and Thalassemic Patients. Mol. Pharmacol. 72, 1111-1123.
120. Spannhoff, A., Machmur, R., Heinke, R., Trojer, P., Bauer, I., Brosch, G., Schule, R., Hanefeld, W., Sippl, W. & Jung, M. (2007). A novel arginine methyltransferase inhibitor with cellular activity. Bioorg. Med. Chem. Lett. 17, 4150-4153.
121. Mai, A., Valente, S., Rotili, D., Massa, S., Botta, G., Brosch, G., Miceli, M., Nebbioso, A. & Altucci, L. (2007). Novel pyrrole-containing histone deacetylase inhibitors endowed with cytodifferentiation activity. Int. J. Biochem. Cell Biol. 39, 1510-1522.
122. Konev, A.Y, Tribus, M., Podhraski, V., Park, S.Y., Lim, C.Y., Emelyanov, A.V., Vershilova, E., Pirrotta, V., Kadonaga, J.T., Lusser, A. & Fyodorov, D.V. (2007). The CHD1 motor protein is required for deposition of histone H3.3 into chromatin in vivo. Science 317, 1087-1090.
123. Ragno, R., Simeoni, S., Rotili, D., Caroli, A., Botta, G., Brosch, G., Massa, S., Mai, A. (2008). Class II-selective histone deacetylase inhibitors. Part 2: Alignment-independent GRIND 3-D QSAR, homology and docking studies. Eur. J. Med. Chem. 43, 621-632.
124. Brosch, G., Loidl, P. & Graessle, S. (2008). Histone Modifications and Chromatin Dynamics: A Focus on Filamentous Fungi. FEMS Microbiol. Rev. 32, 409-439.
125. Mai, A., Valente, S., Cheng, D., Nebbioso, A., Perrone, A., Brosch, G., Sbardella, G., Miceli, M., Altucci, L. & Bedford, M.T. (2008). Epigenetic Multiple Ligands: Mixed Histone/Protein Methyltransferase, Acetyltransferase, and Class III Deacetylase (Sirtuin) Inhibitors. J. Med. Chem. in press.
126. Meraner, J., Lechner, M., Schwarze, F., Gander, R., Jesacher, F. & Loidl, P. (2008). Cell cycle dependent role of HDAC1 for proliferation control through modulating ribosomal DNA transcription. Cell Biol. Int. 32, 1073-1080.
127. Morettini, S., Podhraski, V. & Lusser, A. (2008). ATP-dependent chromatin remodeling enzymes and their various roles in cell cycle control. Front Biosci. 13, 5522-32.
128. Mai A, Cheng D, Bedford MT, Valente S, Nebbioso A, Perrone A, Brosch G, Sbardella G, De Bellis F, Miceli M, Altucci L. (2008). epigenetic multiple ligands: mixed histone/protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhibitors.J Med Chem. 51(7):2279-90.
129. Mai A, Valente S, Nebbioso A, Simeoni S, Ragno R, Massa S, Brosch G, De Bellis F, Manzo F, Altucci L. (2009). New pyrrole-based histone deacetylase inhibitors: binding mode, enzyme- and cell-based investigations.Int J Biochem Cell Biol. 41(1):235-47.
130. Tribus, M., Bauer, I., Galehr, J., Rieser, G., Brosch, G., Loidl, P., Trojer, P., Haas, H. and Graessle, S. (2010). A novel motif in fungal class 1 histone deacetylases is essential for growth and development of Aspergillus. Molecular Biology of the Cell Vol. 21, 345-353.
131. Bauer, I., Graessle, S., Loidl, P., Hohenstein, K., Brosch, G. (2010). Novel insights into the functional role of three protein arginine methyltransferases in Aspergillus nidulans. Fungal Genet Biol. 47(6), 551-561.
132. Castellano, S., Milite, C., Ragno, R., Simeoni, S., Mai, A., Limongelli, V., Novellino, E., Bauer, I., Brosch, G., Spannhoff, A., Cheng, D., Bedford, M.T., Sbardella, G. (2010). Design, synthesis and biological evaluation of carboxy analogues of arginine methyltransferase inhibitor 1 (AMI-1). Chem.Med.Chem. 5(3), 398-414.
133. Schwarze, F., Meraner, J., Lechner, M., Loidl, A., Stasyk, T., Laich, A. & Loidl, P. (2010). Cell cycle dependent acetylation of Rb2/p130 in NIH3T3 cells. Oncogene 29, 5755-5760.
134. Podhraski V, Campo-Fernandez B, Wšrle H, Piatti P, Niederegger H, et al. (2010) CenH3/CID Incorporation Is Not Dependent on the Chromatin Assembly Factor CHD1 in Drosophila. PLoS ONE 5(4): pp. e10120. doi:10.1371/journal.pone.0010120
135. Gourcilleau, D., Bogeat-Triboulot, MB., Le Thiec, D., Lafon-Placette, C., Delaunay, A., Abu El-Soud, W., Brignolas, F., Maury, S. (2010) DNA methylation and histone acetylation: genotypic variations in hybrid poplars, impact of water deficit and relationships with productivity. Annals Forest Sci. 67, 208-218.
136. Morettini, S., Tribus, M., Zeilner, A., Campo-Fernandez, B., Sebald, J., Scheran, G., Wörle, H., Podhraski, V., Fyodorov, D., Lusser, A. (2011). The chromodomains of CHD1 are critical for enzymatic activity but less important for chromatin localization. Nucl. Acids Res., 39(8); 3103-3115.
137. Valente S, Tardugno M, Conte M, Cirilli R, Perrone A, Ragno R, Simeoni S, Tramontano A, Massa S, Nebbioso A, Miceli M, Franci G, Brosch G, Altucci L, Mai A. (2011). Novel Cinnamyl Hydroxyamides and 2-Aminoanilides as Histone Deacetylase Inhibitors: Apoptotic Induction and Cytodifferentiation Activity. Chem. Med. Chem., 6(4),698-712.
138. Saeed, S., Schwarze, F., Loidl, A., Meraner, J., Lechner, M. and Loidl, P. (2012). In vitro phosphorylation and acetylation of the murine pocket protein Rb2/p130. PLoS ONE 7(9): e46174. doi:10.1371/journal.pone.0046174