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Related Concept Videos

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Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
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MEF2C and EBF1 Co-regulate B Cell-Specific Transcription.

Nikki R Kong1,2, Matthew Davis1, Li Chai2

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America.

Plos Genetics
|February 23, 2016
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Summary

Myocyte enhancer factor 2C (MEF2C) is crucial for lymphoid cell development. This study reveals MEF2C partners and mechanisms, including EBF1 and HDAC7, that regulate B cell differentiation and repress myeloid genes.

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Area of Science:

  • Hematology
  • Molecular Biology
  • Immunology

Background:

  • Hematopoietic stem cells differentiate into myeloid, erythroid, and lymphoid lineages.
  • Myocyte enhancer factor 2C (MEF2C) is essential for lymphoid fate decisions, but its mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which MEF2C regulates lymphoid lineage commitment.
  • To identify MEF2C's regulatory partners and downstream targets in B cell differentiation.

Main Methods:

  • Genome-wide survey of MEF2C and early B cell factor-1 (EBF1) binding sites.
  • Analysis of Mef2c knockout mice to assess gene expression changes.
  • Investigation of MEF2C interaction with histone deacetylase 7 (HDAC7).

Main Results:

  • EBF1 identified as a co-regulator with MEF2C, targeting B cell-specific genes.
  • p38 MAPK pathway activation of MEF2C promotes B cell differentiation.
  • Mef2c knockout mice exhibit reduced lymphoid and increased myeloid gene expression.
  • MEF2C interacts with HDAC7 to repress myeloid transcription.

Conclusions:

  • MEF2C acts as a key regulator of lymphoid differentiation through activation and repression mechanisms.
  • EBF1 and HDAC7 are identified as crucial partners in MEF2C-mediated lineage regulation.
  • This study clarifies MEF2C's role in balancing lymphoid and myeloid cell fates.