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MLL1 promotes myogenesis by epigenetically regulating Myf5.

Shufang Cai1, Qi Zhu1, Cilin Guo1

  • 1State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.

Cell Proliferation
|December 17, 2019
PubMed
Summary

Mixed lineage leukaemia protein-1 (MLL1) promotes muscle cell (myoblast) growth and differentiation by epigenetically regulating the Myf5 gene. This epigenetic regulation involves histone 3 lysine 4 trimethylation (H3K4me3) on the Myf5 promoter, crucial for muscle repair.

Keywords:
H3K4me3MLL1Myf5myogenesisproliferation

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Developmental Biology

Background:

  • Mixed lineage leukaemia protein-1 (MLL1) is a key epigenetic regulator involved in histone methylation.
  • MLL1 plays critical roles in embryonic development and hematopoiesis.
  • Previous studies suggest MLL1 expression correlates with myogenic ability in pigs.

Purpose of the Study:

  • To investigate the roles of MLL1 in myogenesis (muscle development).
  • To explore the regulatory mechanisms of MLL1 in muscle cell differentiation and proliferation.

Main Methods:

  • MLL1 expression was manipulated in C2C12 myoblasts using siRNA.
  • Assays included EdU, cell cycle, immunofluorescence, qRT-PCR, and Western blot to assess proliferation and differentiation.
  • Chromatin immunoprecipitation (ChIP) assay was used to detect H3K4me3 enrichment on the Myf5 promoter.
  • A cardiotoxin-induced muscle regeneration model was employed for in vivo studies.

Main Results:

  • MLL1 expression was high in proliferating C2C12 cells and decreased upon differentiation.
  • MLL1 knockdown inhibited myoblast proliferation, impaired differentiation, and caused G1 cell cycle arrest.
  • MLL1 knockdown led to decreased expression of Myf5 and Cyclin D1.
  • MLL1 epigenetically regulated Myf5 expression via H3K4me3 on its promoter.
  • In vivo, MLL1 was essential for Pax7-positive satellite cell proliferation and muscle repair.

Conclusions:

  • MLL1 facilitates myoblast proliferation and differentiation.
  • MLL1 epigenetically regulates Myf5 expression through H3K4me3.
  • MLL1 is crucial for the proliferation of Pax7-positive satellite cells and muscle regeneration.