Article ID Journal Published Year Pages File Type
1946697 Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2011 7 Pages PDF
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.

Research Highlights► The DNA binding transcriptional repressor Gfi1 binds to the p150 subunit of the histone chaperone Caf-1. ► Both Gfi1 and Caf-1 co-localize in human cell nuclei. ► Caf-1 is required for the transcriptional repressor activity of Gfi1. ► Caf-1 is recruited to Gfi1 target gene promoters. ► Caf-1 is contained in a larger repressor complex that contains Gfi1 and histone modifying enzymes such as HDAC1 and LSD1.

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