Sin3: a flexible regulator of global gene expression and genome stability
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SIN3 was first identified genetically as a global regulator of transcription. Sin3 is a large protein composed mainly of protein-interaction domains, whose function is to provide structural support for a heterogeneous Sin3/histone deacetylase (HDAC) complex. The core Sin3/HDAC complex is conserved from yeast to man and consists of eight proteins. In addition to HDACs, Sin3 can sequester other enzymatic functions, including nucleosome remodeling, DNA methylation, N-acetylglucoseamine transferase activity, and histone methylation. Since the Sin3/HDAC complex lacks any DNA-binding activity, it must be targeted to gene promoters by interacting with DNA-binding proteins. Although most research on Sin3 has focused on its role as a corepressor, mounting evidence suggests that Sin3 can also positively regulate transcription. Furthermore, Sin3 is key to the propagation of epigenetically silenced domains and is required for centromere function. Thus, Sin3 provides a platform to deliver multiple combinations modifications to the chromatin, using both sequence-specific and sequence-independent mechanisms.
KeywordsSIN3 Histone acetylation Chromatin Gene regulation Corepressor
K.E. is a Royal Swedish Academy of Sciences Research Fellow supported by grants from the Knut and Alice Wallenberg Foundation, the Swedish Cancer Society, and the Swedish Research Councils VR-M, VR-NT and SSF. We would like to thank Mattias Mannervik and Julian Walfridsson for their helpful comments on the manuscript.
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