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Hdac6 regulates Tip60-p400 function in stem cells.

Poshen B Chen1, Jui-Hung Hung, Taylor L Hickman

  • 1Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, United States.

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|December 5, 2013
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Summary
This summary is machine-generated.

Histone deacetylase 6 (Hdac6) is crucial for embryonic stem cell (ESC) proliferation and differentiation by modulating the Tip60-p400 complex. Hdac6

Keywords:
Hdac6Kat5Tip60chromatinstem cells

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Area of Science:

  • Epigenetics and Gene Regulation
  • Stem Cell Biology
  • Chromatin Remodeling

Background:

  • Embryonic stem cells (ESCs) rely on the Tip60 histone acetyltransferase for proliferation and differentiation control.
  • The class II histone deacetylase Hdac6 is typically cytoplasmic in differentiated cells but its role in ESCs is less understood.

Purpose of the Study:

  • To investigate the function and localization of Hdac6 in ESCs.
  • To determine the relationship between Hdac6 and the Tip60-p400 complex in stem cells.
  • To elucidate Hdac6's role in regulating gene expression and differentiation in ESCs.

Main Methods:

  • Co-immunoprecipitation to identify protein interactions.
  • Immunofluorescence microscopy to determine protein localization.
  • Chromatin immunoprecipitation followed by sequencing (ChIP-seq) to map gene promoter occupancy.
  • Gene expression analysis to assess regulatory roles.

Main Results:

  • Hdac6 co-purifies with the Tip60-p400 complex in ESCs.
  • Hdac6 is predominantly nuclear in ESCs, neural stem cells, and some cancer cell lines, interacting with Tip60-p400.
  • Hdac6 is essential for the regulation of Tip60-p400 target genes, particularly those repressed by the complex.
  • Hdac6 localizes to promoters bound by Tip60-p400 and is required for Tip60-p400 binding, rather than histone deacetylation.
  • Hdac6 is necessary for robust ESC differentiation, similar to canonical Tip60-p400 subunits.

Conclusions:

  • Hdac6 plays a significant role in modulating Tip60-p400 complex function within stem cells.
  • Nuclear Hdac6 is critical for maintaining stem cell pluripotency and regulating differentiation pathways.
  • The findings reveal a novel mechanism of epigenetic regulation involving Hdac6 and the Tip60-p400 complex in stem cell biology.