title: Family with sequence similarity 60A (FAM60A) protein is a cell cycle-fluctuating regulator of the SIN3-HDAC1 histone deacetylase complex.
abstract: 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.
authors.affiliation: Medical Research Council Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Muñoz
authors.forename: Thomas
authors.initials: T
authors.lastname: MacArtney
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Pulido
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.forename: Sonia
authors.initials: S
authors.lastname: Rocha
authors.forename: John
authors.initials: J
authors.lastname: Rouse
mesh_terms: D000107:Acetylation; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D016193:G1 Phase / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics; D016196:S Phase / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000235:genetics / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; D021122:Protein Subunits; C576636:SINHCAF protein, human; D019938:Cyclin D1; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex