The Effects of Inappropriate Inheritance of Histone Methylation on Muscle Structure and Function
Disciplines
Cell and Developmental Biology
Abstract (300 words maximum)
At fertilization, maternally deposited histone modifying enzymes establish germline versus somatic transcriptional states by adding and removing histone methylation. To do this in C. elegans, the H3K4 demethylase, SPR-5, removes active H3K4 methylation, while the H3K9 methyltransferase, MET-2, adds repressive H3K9 methylation to prevent germline gene expression in the soma. Recent studies show that SPR-5; MET-2 maternal reprogramming is antagonized by the H3K36 methyltransferase, MES-4, which maintains H3K36 methylation at germline genes to ensure proper germline gene expression in germ cells. Maternal loss of SPR-5 and MET-2 allows MES-4 to maintain H3K36 methylation at germline genes in the soma leading to ectopic expression of germline genes and developmental phenotypes including muscle defects. Here, we show that muscle morphology and function are compromised in spr-5, met-2 mutants, but can be rescued by knocking down MES-4. We also show that late generation spr-5 and met-2 single mutants display increased muscle disorganization that does not correlate with decreased motility. Together, our data provide insights into how mis inherited histone methylation affects muscle function.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Brandon Carpenter
The Effects of Inappropriate Inheritance of Histone Methylation on Muscle Structure and Function
At fertilization, maternally deposited histone modifying enzymes establish germline versus somatic transcriptional states by adding and removing histone methylation. To do this in C. elegans, the H3K4 demethylase, SPR-5, removes active H3K4 methylation, while the H3K9 methyltransferase, MET-2, adds repressive H3K9 methylation to prevent germline gene expression in the soma. Recent studies show that SPR-5; MET-2 maternal reprogramming is antagonized by the H3K36 methyltransferase, MES-4, which maintains H3K36 methylation at germline genes to ensure proper germline gene expression in germ cells. Maternal loss of SPR-5 and MET-2 allows MES-4 to maintain H3K36 methylation at germline genes in the soma leading to ectopic expression of germline genes and developmental phenotypes including muscle defects. Here, we show that muscle morphology and function are compromised in spr-5, met-2 mutants, but can be rescued by knocking down MES-4. We also show that late generation spr-5 and met-2 single mutants display increased muscle disorganization that does not correlate with decreased motility. Together, our data provide insights into how mis inherited histone methylation affects muscle function.