The effects of inappropriate inheritance of histone methylation on muscle function
Disciplines
Cell and Developmental Biology
Abstract (300 words maximum)
Histone methylation, a post-transcriptional modification occurring on the N-terminal tails of histone core proteins, plays a crucial role in regulating DNA accessibility and, consequently, gene expression. Histone methylation, orchestrated by enzymes like SPR-5 and MET-2, is a critical regulator of gene expression and cellular function. In the nematode C. elegans, these enzymes play pivotal roles in maternal reprogramming and ensuring the proper epigenetic landscape during embryonic development. H3K4me (a modification associated with active transcription) is removed by the H3K4 demethylase, SPR-5, and H3K9me (a modification associated with transcriptional repression) is subsequently added by the histone methyltransferase, MET-2. It was demonstrated that SPR-5; MET-2 maternal reprogramming antagonizes the H3K36 methyltransferase MES-4, which maintains transcriptional memory for a subset of germline genes across generations. As the maternal loss of SPR-5 and MET-2 results in ectopic expression of MES-4 germline genes in somatic tissues this results in developmental delay and an impairment in muscle motility. It was recently found that spr-5; met-2 double mutants demonstrated defects in muscle motility. This finding led us to investigate whether spr-5 and met-2 single mutants also display a defect in muscle motility. Interestingly, the spr-5 mutants, but not met-2 demonstrated a defect in muscle motility but not to the extent of spr-5; met-2 mutants. This data suggests that met-2 may have a more specific role in muscle development and/or function. Using motility assays, we are also testing whether there is a decline in muscle motility from early, middle, to late generations in spr-5 and met-2 mutants that progressively inherit inappropriate histone methylation. We hypothesize that muscle function will decline from early to late generations. This data will provide insights into how mutations in the highly conserved maternal reprogramming enzymes affect the muscle and result in tissue-specific phenotypes throughout development.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Dr. Brandon Carpenter
The effects of inappropriate inheritance of histone methylation on muscle function
Histone methylation, a post-transcriptional modification occurring on the N-terminal tails of histone core proteins, plays a crucial role in regulating DNA accessibility and, consequently, gene expression. Histone methylation, orchestrated by enzymes like SPR-5 and MET-2, is a critical regulator of gene expression and cellular function. In the nematode C. elegans, these enzymes play pivotal roles in maternal reprogramming and ensuring the proper epigenetic landscape during embryonic development. H3K4me (a modification associated with active transcription) is removed by the H3K4 demethylase, SPR-5, and H3K9me (a modification associated with transcriptional repression) is subsequently added by the histone methyltransferase, MET-2. It was demonstrated that SPR-5; MET-2 maternal reprogramming antagonizes the H3K36 methyltransferase MES-4, which maintains transcriptional memory for a subset of germline genes across generations. As the maternal loss of SPR-5 and MET-2 results in ectopic expression of MES-4 germline genes in somatic tissues this results in developmental delay and an impairment in muscle motility. It was recently found that spr-5; met-2 double mutants demonstrated defects in muscle motility. This finding led us to investigate whether spr-5 and met-2 single mutants also display a defect in muscle motility. Interestingly, the spr-5 mutants, but not met-2 demonstrated a defect in muscle motility but not to the extent of spr-5; met-2 mutants. This data suggests that met-2 may have a more specific role in muscle development and/or function. Using motility assays, we are also testing whether there is a decline in muscle motility from early, middle, to late generations in spr-5 and met-2 mutants that progressively inherit inappropriate histone methylation. We hypothesize that muscle function will decline from early to late generations. This data will provide insights into how mutations in the highly conserved maternal reprogramming enzymes affect the muscle and result in tissue-specific phenotypes throughout development.