SCIENCE@home

Hemizygous mutation of Jmjd3 in muscle stem cells increases H3K27 methylation on Pax7 leading to impaired myogenesis.

J. Tidball,Lina Petrossian,Cynthia M McKee,Michelle Wehling-Henricks

Published 2025 in American Journal of Physiology - Cell Physiology

ABSTRACT

Development of myogenic cells, called satellite cells, is determined by transcription factors that regulate their quiescence (e.g. Pax7), activation (e.g. MyoD) and terminal differentiation (e.g., myogenin). Demethylation of lysine 3 on histone 27 (H3K27) activates expression of Myod and Myog. In this investigation, we investigated the effects of a satellite-cell-targeted, hemizygous mutation of the H3K27 demethylase Jmjd3 in healthy muscle. Using sequencing of chromatin fragments precipitated from Jmjd3 mutant and control satellite cells using anti-H3K27me3, we found that the Pax7 promoter was the only chromatin that experienced significantly increased H3K27 methylation in mutant cells. However, RNA sequencing showed that 143 genes were down-regulated in mutant cells, including Myod, a direct target of Pax7, and at least 72 other genes that contained E-boxes targeted by MyoD. Gene ontology analysis showed enrichment of genes involved in myogenesis in the down-regulated genes. Reduced expression of Pax7, Myod, and Myog was confirmed by QPCR, western blots and immunohistochemistry. Mutant muscles also had smaller diameter fibers, fewer myonuclei and diminished myogenic cell fusion, indicating impaired growth and differentiation. These findings show that Jmjd3 affects demethylation of H3K27 at the Pax7 promoter and increased H3K27 methylation reduces expression of Pax7 and its target genes, disrupting muscle growth.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-45 of 45 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1