MEF2C and EBF1 Co-regulate B Cell-Specific Transcription
Hematopoietic stem cells are capable of self-renewal or differentiation along three main lineages: myeloid, erythroid, and lymphoid. One of the earliest lineage decisions for blood progenitor cells is whether to adopt the lymphoid or myeloid fate. Previous work had shown that myocyte enhancer factor...
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Public Library of Science
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762780/ |
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pubmed-47627802016-03-07 MEF2C and EBF1 Co-regulate B Cell-Specific Transcription Kong, Nikki R. Davis, Matthew Chai, Li Winoto, Astar Tjian, Robert Research Article Hematopoietic stem cells are capable of self-renewal or differentiation along three main lineages: myeloid, erythroid, and lymphoid. One of the earliest lineage decisions for blood progenitor cells is whether to adopt the lymphoid or myeloid fate. Previous work had shown that myocyte enhancer factor 2C (MEF2C) is indispensable for the lymphoid fate decision, yet the specific mechanism of action remained unclear. Here, we have identified early B cell factor-1 (EBF1) as a co-regulator of gene expression with MEF2C. A genome-wide survey of MEF2C and EBF1 binding sites identified a subset of B cell-specific genes that they target. We also determined that the p38 MAPK pathway activates MEF2C to drive B cell differentiation. Mef2c knockout mice showed reduced B lymphoid-specific gene expression as well as increased myeloid gene expression, consistent with MEF2C’s role as a lineage fate regulator. This is further supported by interaction between MEF2C and the histone deacetylase, HDAC7, revealing a likely mechanism to repress the myeloid transcription program. This study thus elucidates both activation and repression mechanisms, identifies regulatory partners, and downstream targets by which MEF2C regulates lymphoid-specific differentiation. Public Library of Science 2016-02-22 /pmc/articles/PMC4762780/ /pubmed/26900922 http://dx.doi.org/10.1371/journal.pgen.1005845 Text en © 2016 Kong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kong, Nikki R. Davis, Matthew Chai, Li Winoto, Astar Tjian, Robert |
| spellingShingle |
Kong, Nikki R. Davis, Matthew Chai, Li Winoto, Astar Tjian, Robert MEF2C and EBF1 Co-regulate B Cell-Specific Transcription |
| author_facet |
Kong, Nikki R. Davis, Matthew Chai, Li Winoto, Astar Tjian, Robert |
| author_sort |
Kong, Nikki R. |
| title |
MEF2C and EBF1 Co-regulate B Cell-Specific Transcription |
| title_short |
MEF2C and EBF1 Co-regulate B Cell-Specific Transcription |
| title_full |
MEF2C and EBF1 Co-regulate B Cell-Specific Transcription |
| title_fullStr |
MEF2C and EBF1 Co-regulate B Cell-Specific Transcription |
| title_full_unstemmed |
MEF2C and EBF1 Co-regulate B Cell-Specific Transcription |
| title_sort |
mef2c and ebf1 co-regulate b cell-specific transcription |
| description |
Hematopoietic stem cells are capable of self-renewal or differentiation along three main lineages: myeloid, erythroid, and lymphoid. One of the earliest lineage decisions for blood progenitor cells is whether to adopt the lymphoid or myeloid fate. Previous work had shown that myocyte enhancer factor 2C (MEF2C) is indispensable for the lymphoid fate decision, yet the specific mechanism of action remained unclear. Here, we have identified early B cell factor-1 (EBF1) as a co-regulator of gene expression with MEF2C. A genome-wide survey of MEF2C and EBF1 binding sites identified a subset of B cell-specific genes that they target. We also determined that the p38 MAPK pathway activates MEF2C to drive B cell differentiation. Mef2c knockout mice showed reduced B lymphoid-specific gene expression as well as increased myeloid gene expression, consistent with MEF2C’s role as a lineage fate regulator. This is further supported by interaction between MEF2C and the histone deacetylase, HDAC7, revealing a likely mechanism to repress the myeloid transcription program. This study thus elucidates both activation and repression mechanisms, identifies regulatory partners, and downstream targets by which MEF2C regulates lymphoid-specific differentiation. |
| publisher |
Public Library of Science |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762780/ |
| _version_ |
1613541719158030336 |