title: The p150 subunit of the histone chaperone Caf-1 interacts with the transcriptional repressor Gfi1.
abstract: Modification of histones is critically involved in regulating chromatin structure and gene expression. The zinc finger protein Gfi1 silences transcription by recruiting a complex of histone modifying enzymes such as LSD-1/CoRest and HDAC-1 to target gene promoters. Here we present evidence that Gfi1 forms a complex with the p150 subunit of the histone chaperone chromatin assembly factor-1 (Caf-1). Gfi1 and p150 interact at endogenous expression levels and co-localize in distinct sub-nuclear structures. We show that p150 enhances Gfi1-mediated transcriptional repression and that it occupies Gfi1 target gene promoters in transfected cells and primary murine T cells only in the presence of Gfi1. Finally, size exclusion chromatography shows a fraction of p150 to coelute with Gfi1, LSD-1 and HDAC-1 and thus provides evidence that p150 is part of the Gfi1 repression complex. Since p150 binds directly to histones H3 and H4, our findings suggest that p150 may link the DNA-bound Gfi1 repressor complex to histones enabling modifications required for transcriptional silencing.
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM), H2W 1R7, Montréal, QC, Canada.
authors.forename: Florian
authors.initials: F
authors.lastname: Heyd
authors.forename: Riyan
authors.initials: R
authors.lastname: Chen
authors.forename: Khashayar
authors.initials: K
authors.lastname: Afshar
authors.forename: Ingrid
authors.initials: I
authors.lastname: Saba
authors.forename: Claude
authors.initials: C
authors.lastname: Lazure
authors.forename: Katharina
authors.initials: K
authors.lastname: Fiolka
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
mesh_terms: D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D056504:Chromatin Assembly Factor-1 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018922:HL-60 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D056504:Chromatin Assembly Factor-1; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D014157:Transcription Factors