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The SIN3A-HDAC complex deacetylates histones thereby repressing gene transcription. Here we describe family with sequence similarity 60A (FAM60A), a cell cycle-regulated protein that binds to the SIN3-HDAC complex. FAM60A expression peaks during G(1) and S phases of the cell cycle in U2OS cells, in a manner similar to the G(1) regulator cyclin D1, which is a known target of SIN3-HDAC. In this light we found that FAM60A binds to SIN3-HDAC-regulated promoters such as cyclin D1 in G(1) and S phases. Cells depleted of FAM60A show increased histone acetylation at the cyclin D1 promoter and elevated levels of cyclin D1 mRNA and protein. Furthermore, depletion of FAM60A altered the periodic association of HDAC1 with the cyclin D1 promoter, increased cyclin D1 expression at all cell cycle phases, and caused premature S phase entry. The data in this study introduce FAM60A as a novel regulator of SIN3-HDAC function and gene expression.

Original publication

DOI

10.1074/jbc.M112.382499

Type

Journal article

Journal

J Biol Chem

Publication Date

21/09/2012

Volume

287

Pages

32346 - 32353

Keywords

Acetylation, Cyclin D1, DNA-Binding Proteins, G1 Phase, Gene Expression Regulation, HEK293 Cells, Histone Deacetylase 1, Humans, Protein Binding, Protein Subunits, S Phase, Sin3 Histone Deacetylase and Corepressor Complex