Direct Interactions of OCA-B and TFII-I Regulate Immunoglobulin Heavy-Chain Gene Transcription by Facilitating Enhancer-Promoter Communication

作者：Ren Xiaodi; Siegel Rachael; Kim Unkyu; Roeder Robert G^*

来源：Molecular Cell, 2011, 42(3): 342-355.

DOI：10.1016/j.molcel.2011.04.011

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.

• 出版日期2011-5-6