PUBLICATION

The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation

Authors
Huang, Y.C., Shih, H.Y., Lin, S.J., Chiu, C.C., Ma, T.L., Yeh, T.H., Cheng, Y.C.
ID
ZDB-PUB-141007-3
Date
2015
Source
Developmental Neurobiology   75(5): 452-62 (Journal)
Registered Authors
Lin, Sheng-Jia
Keywords
Kmt2a, differentiation, neural progenitors, proliferation, zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation/physiology*
  • Cell Proliferation*
  • Gene Expression Regulation, Developmental/physiology*
  • Histone-Lysine N-Methyltransferase/metabolism*
  • Neural Stem Cells/cytology*
  • Neurogenesis/physiology*
  • Neuroglia/cytology*
  • Neurons/physiology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed
25284327 Full text @ Dev. Neurobiol.
Abstract
Multiple epigenetic factors play a critical role in cell proliferation and differentiation. However, their function in embryogenesis, especially in neural development, is currently unclear. The Trithorax group (TrxG) homolog KMT2A (MLL1) is an important epigenetic regulator during development and has an especially well-defined role in hematopoiesis. Translocation and aberrant expression of KMT2A is often observed in many tumors, indicating its proto-oncogenic character. Here, we show that Kmt2a was essential for neural development in zebrafish embryos. Disrupting the expression of Kmt2a using morpholino antisense oligonucleotides and a dominant-negative variant resulted in neurogenic phenotypes, including downregulated proliferation of neural progenitors, premature differentiation of neurons and impaired gliogenesis. This study therefore revealed a novel function of Kmt2a in cell proliferation and differentiation, providing further insight into the function of TrxG proteins in neural development and brain tumors.
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Human Disease / Model
Sequence Targeting Reagents
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Antibodies
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Mapping