Sin Meets NuRD and Other Tails of Repression

Abstract

Why are there multiple HDAC corepressor complexes? Although the mSin3 and Mi-2/NuRD complexes could be redundant, it is difficult to imagine the high degree of evolutionary conservation of two such multicomponent systems unless some aspects of their function are unique. Indeed both the chromatin remodeling activity associated with Mi-2/NuRD as well as the distinct transcription factors present in both corepressor complexes point toward specialization. Perhaps Mi-2/NuRD target genes are predominantly localized in relatively closed regions of chromatin, thus requiring a nucleosome remodeling step for access of Mi-2/NuRD to histones and subsequent or concomitant deacetylation (see Tyler and Kadonaga 1999xTyler, J.K and Kadonaga, J.T. Cell. 1999; 99: 443–446Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesTyler and Kadonaga 1999). Such genes might be resistant to Sin3-mediated repression, which would be reserved for previously remodeled actively transcribed genes that may not require further chromatin remodeling for deacetylation such as HO in yeast (8xKrebs, J.E, Kuo, M.H, Allis, C.D, and Peterson, C.L. Genes Dev. 1999; 13: 1412–1421Crossref | PubMedSee all References, 3xCosma, M.P, Tanaka, T, and Nasmyth, K. Cell. 1999; 97: 299–311Abstract | Full Text | Full Text PDF | PubMed | Scopus (548)See all References). There is also compelling evidence that certain silenced regions of chromatin may occupy nuclear compartments distinct from those in which active genes reside. Therefore, it is possible that the Mi-2/NuRD (or, for that matter, any of the other corepressors mentioned above) may possess activities that facilitate relocalization of targeted genetic regions to specific nuclear domains (see Sun and Elgin 1999xSun, F.L and Elgin, S.C.R. Cell. 1999; 99: 459–462Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesSun and Elgin 1999 [this issue of Cell]).In a general sense, the mechanism of repression is likely to have gene-specific aspects even though much of the regulatory machinery involved is common to all genes. Different corepressors may be thought of as acting to unleash HDAC activities at the target site in distinct ways. For example, some corepressors may tether HDAC to the complex while others may release HDAC in the vicinity of the gene target. The interplay between different types of chromatin modifications including deacetylation, methylation, and chromatin remodeling may be coordinated through the functions of corepressors (see Bird and Wolffe 1999xBird, A.P and Wolffe, A.P. Cell. 1999; 99: 451–454Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesBird and Wolffe 1999 and Tyler and Kadonaga 1999xTyler, J.K and Kadonaga, J.T. Cell. 1999; 99: 443–446Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesTyler and Kadonaga 1999). Moreover, the recent work on corepressors has illuminated a profound connection between transcriptional repression and fundamental aspects of cell biology including proliferation, differentiation, and cancer.*To whom correspondence should be addressed (e-mail: eisenman@fhcrc.org).