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https://hdl.handle.net/2440/133538
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Type: | Journal article |
Title: | A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters |
Author: | Hatzi, K. Jiang, Y. Huang, C. Garrett-Bakelman, F. Gearhart, M.D. Giannopoulou, E.G. Zumbo, P. Kirouac, K. Bhaskara, S. Polo, J.M. Kormaksson, M. MacKerell, A.D. Xue, F. Mason, C.E. Hiebert, S.W. Prive, G.G. Cerchietti, L. Bardwell, V.J. Elemento, O. Melnick, A. |
Citation: | Cell Reports, 2013; 4(3):578-588 |
Publisher: | Cell Press |
Issue Date: | 2013 |
ISSN: | 2211-1247 2211-1247 |
Statement of Responsibility: | Katerina Hatzi, Yanwen Jiang, Chuanxin Huang, Francine Garrett-Bakelman, Micah D.Gearhart, Eugenia G.Giannopoulou |
Abstract: | The BCL6 transcriptional repressor is required for the development of germinal center (GC) B cells and diffuse large B cell lymphomas (DLBCLs). Although BCL6 can recruit multiple corepressors, its transcriptional repression mechanism of action in normal and malignant B cells is unknown. We find that in B cells, BCL6 mostly functions through two independent mechanisms that are collectively essential to GC formation and DLBCL, both mediated through its N-terminal BTB domain. These are (1) the formation of a unique ternary BCOR-SMRT complex at promoters, with each corepressor binding to symmetrical sites on BCL6 homodimers linked to specific epigenetic chromatin features, and (2) the "toggling" of active enhancers to a poised but not erased conformation through SMRT-dependent H3K27 deacetylation, which is mediated by HDAC3 and opposed by p300 histone acetyltransferase. Dynamic toggling of enhancers provides a basis for B cells to undergo rapid transcriptional and phenotypic changes in response to signaling or environmental cues. |
Keywords: | B-Lymphocytes |
Rights: | This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative WorksLicense, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source arecredited |
DOI: | 10.1016/j.celrep.2013.06.016 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.1016/j.celrep.2013.06.016 |
Appears in Collections: | Medical Sciences publications |
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hdl_133538.pdf | Published version | 2.24 MB | Adobe PDF | View/Open |
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