title: Direct interactions of OCA-B and TFII-I regulate immunoglobulin heavy-chain gene transcription by facilitating enhancer-promoter communication.
abstract: B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in Igh promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3' enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3' enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Ren
authors.forename: Rachael
authors.initials: R
authors.lastname: Siegel
authors.forename: Unkyu
authors.initials: U
authors.lastname: Kim
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D034622:RNA Interference; D012091:Repetitive Sequences, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D007143:Immunoglobulin Heavy Chains; D015534:Trans-Activators; D019473:Transcription Factors, TFII; D000099186:Histone Deacetylase 3; C104259:GTF2I protein, human; C091546:POU2AF1 protein, human