Hassig C A, Fleischer T C, Billin A N, Schreiber S L, Ayer D E
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Cell. 1997 May 2;89(3):341-7. doi: 10.1016/s0092-8674(00)80214-7.
Members of the Mad family of bHLH-Zip proteins heterodimerize with Max to repress transcription in a sequence-specific manner. Transcriptional repression by Mad:Max heterodimers is mediated by ternary complex formation with either of the corepressors mSin3A or mSin3B. We report here that mSin3A is an in vivo component of large, heterogeneous multiprotein complexes and is tightly and specifically associated with at least seven polypeptides. Two of the mSin3A-associated proteins, p50 and p55, are highly related to the histone deacetylase HDAC1. The mSin3A immunocomplexes possess histone deacetylase activity that is sensitive to the specific deacetylase inhibitor trapoxin. mSin3A-targeted repression of a reporter gene is reduced by trapoxin treatment, suggesting that histone deacetylation mediates transcriptional repression through Mad-Max-mSin3A multimeric complexes.
bHLH-Zip蛋白Mad家族的成员与Max形成异源二聚体，以序列特异性方式抑制转录。Mad:Max异源二聚体介导的转录抑制是通过与共抑制因子mSin3A或mSin3B形成三元复合物来实现的。我们在此报告，mSin3A是大型异质性多蛋白复合物的体内组成成分，并且与至少七种多肽紧密且特异性地相关联。两种与mSin3A相关的蛋白，p50和p55，与组蛋白脱乙酰基酶HDAC1高度相关。mSin3A免疫复合物具有对特异性脱乙酰基酶抑制剂曲古抑菌素敏感的组蛋白脱乙酰基酶活性。曲古抑菌素处理可降低mSin3A靶向的报告基因的抑制作用，这表明组蛋白去乙酰化通过Mad-Max-mSin3A多聚体复合物介导转录抑制。
