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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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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
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HDAC4 regulates muscle fiber type-specific gene expression programs.

Todd J Cohen1,2, Moon-Chang Choi1, Meghan Kapur1

  • 1Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Molecules and Cells
|March 3, 2015
PubMed
Summary
This summary is machine-generated.

HDAC4

Keywords:
HDAC4MEF2PGC-1αfiber type

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Area of Science:

  • Muscle biology
  • Molecular biology
  • Transcriptional regulation

Background:

  • Muscle fiber types (fast/glycolytic and slow/oxidative) have distinct functionalities.
  • MEF2 transcription factors control fiber type-specific programs.
  • HDAC4 acts as a MEF2 inhibitor, influencing muscle function.

Purpose of the Study:

  • To investigate the role of HDAC4 localization and phosphorylation in determining muscle fiber type.
  • To understand how HDAC4 regulates the oxidative metabolic gene program.

Main Methods:

  • Immunofluorescence to determine HDAC4 localization in different fiber types.
  • Biochemical assays to assess HDAC4 phosphorylation.
  • Genetic reprogramming of muscle fibers using CaMKII and calcineurin.

Main Results:

  • HDAC4 is nuclear in fast/glycolytic fibers and cytoplasmic in slow/oxidative fibers.
  • Cytoplasmic localization of HDAC4 correlates with its hyper-phosphorylation in slow/oxidative fibers.
  • Genetic reprogramming induces HDAC4 phosphorylation, nuclear export, and oxidative fiber markers.
  • HDAC4 represses the MEF2-dependent, PGC-1α-mediated oxidative gene program.

Conclusions:

  • Differential phosphorylation and subcellular localization of HDAC4 are critical for establishing muscle fiber type-specific transcriptional programs.
  • HDAC4 acts as a key regulator linking signaling pathways to metabolic gene expression in muscle.