Examination of how inappropriate inheritance of histone methylation affects muscle function

Disciplines

Developmental Biology

Abstract (300 words maximum)

Histone methylation is a post-transcriptional modification to the N-terminal tails of histone core proteins that regulates DNA accessibility, and consequently, gene expression. Like DNA, histone methylation can be inherited between generations, and is highly regulated during embryonic development. At fertilization, histone methylation must undergo maternal reprogramming to reset the epigenetic landscape in the new zygote. During maternal reprogramming of histone methylation in C. elegans, 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. Recently, we demonstrated that SPR- 5; MET-2 maternal reprogramming antagonizes the H3K36 methyltransferase, MES-4, which maintains a transcriptional memory of a subset of germline genes between generations. Maternal loss of SPR-5 and MET-2 results in ectopic expression of MES-4 germline genes in somatic tissues and a range of severe developmental phenotypes. One of these severe developmental phenotypes is defects in body wall muscle morphology. As part of a curriculum-based undergraduate research experience (CURE) implemented in Developmental Biology (BIOL_4390K), students performed muscle motility assays to examine of inappropriately inherited H3K4me2 affect muscle function. Data from this CURE will be integrated into ongoing research in the Carpenter Lab aimed at understanding how inappropriate inheritance of chromatin states affect normal development. Our findings will provide insights into how aberrant soma-to-germline transition leads to complex developmental phenotypes that overlap with human patients harboring mutations in these same enzymes.

Academic department under which the project should be listed

CSM - Molecular and Cellular Biology

Primary Investigator (PI) Name

Brandon Carpenter

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Examination of how inappropriate inheritance of histone methylation affects muscle function

Histone methylation is a post-transcriptional modification to the N-terminal tails of histone core proteins that regulates DNA accessibility, and consequently, gene expression. Like DNA, histone methylation can be inherited between generations, and is highly regulated during embryonic development. At fertilization, histone methylation must undergo maternal reprogramming to reset the epigenetic landscape in the new zygote. During maternal reprogramming of histone methylation in C. elegans, 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. Recently, we demonstrated that SPR- 5; MET-2 maternal reprogramming antagonizes the H3K36 methyltransferase, MES-4, which maintains a transcriptional memory of a subset of germline genes between generations. Maternal loss of SPR-5 and MET-2 results in ectopic expression of MES-4 germline genes in somatic tissues and a range of severe developmental phenotypes. One of these severe developmental phenotypes is defects in body wall muscle morphology. As part of a curriculum-based undergraduate research experience (CURE) implemented in Developmental Biology (BIOL_4390K), students performed muscle motility assays to examine of inappropriately inherited H3K4me2 affect muscle function. Data from this CURE will be integrated into ongoing research in the Carpenter Lab aimed at understanding how inappropriate inheritance of chromatin states affect normal development. Our findings will provide insights into how aberrant soma-to-germline transition leads to complex developmental phenotypes that overlap with human patients harboring mutations in these same enzymes.