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Atrophin recruits HDAC1/2 and G9a to modify histone H3K9 and to determine cell fates
Author(s) -
Wang Lei,
Charroux Bernard,
Kerridge Stephen,
Tsai ChihCheng
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.67
Subject(s) - biology , histone , histone methyltransferase , genetics , histone h3 , hdac1 , microbiology and biotechnology , methylation , histone h2a , gene , histone deacetylase
Atrophin family proteins, including the vertebrate arginine–glutamic acid dipeptide repeats protein (RERE) and Drosophila Atrophin (Atro), constitute a new class of nuclear receptor corepressors. Both RERE and Atro share the ELM2 (EGL‐27 and MTA1 homology 2) and SANT (SWI3/ADA2/N‐CoR/TFIII‐B) domains, which are also present in other important transcriptional cofactors. Here, we report that the SANT domain in RERE binds to the histone methyltransferase G9a, and that both the ELM2 and SANT domains orchestrate molecular events that lead to a stable methylation of histone H3‐lysine 9. We establish the physiological relevance of these interactions among Atrophin, G9a, and histone deacetylases 1 and 2 in Drosophila by showing that these proteins localize to overlapping chromosomal loci, and act together to suppress wing vein and melanotic‐mass formation. This study not only shows a new function of the SANT domain and establishes its connection with the ELM2 domain, but also implies that a similar strategy is used by other ELM2–SANT proteins to repress gene transcription and to exert biological effects.