Examining the developmental effects of knocking down S-adenosylmethionine synthases in spr-5 mutants that fail to properly inherit chromatin states
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. Loss of either SPR-5 or MET-2 leads to progressive accumulation of H3K4me2 over generations that correlates with sterility and slight developmental delay. Recently, S-adenosylmethionine synthases, SAMS-1 and SAMS-4, which are critical enzymes in a biochemical pathway that generates the methyl donor S-adenosylmethionine (SAM), were shown to regulate distinct populations of H3K4me during stress response. These findings raise the interesting possibility that SAMS-1 and SAMS-4 may affect development in spr-5 and met-2 mutants that inherit increased aberrant levels of H3K4me. To test this in a curriculum-based undergraduate research experience (CURE) implemented in Developmental Biology (BIOL_4390K), students performed developmental progression assays on spr-5 and met-2 single mutants after knocking down either SAMS-1 or SAMS-4 via RNA interference (RNAi). 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.
Examining the developmental effects of knocking down S-adenosylmethionine synthases in spr-5 mutants that fail to properly inherit chromatin states
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. Loss of either SPR-5 or MET-2 leads to progressive accumulation of H3K4me2 over generations that correlates with sterility and slight developmental delay. Recently, S-adenosylmethionine synthases, SAMS-1 and SAMS-4, which are critical enzymes in a biochemical pathway that generates the methyl donor S-adenosylmethionine (SAM), were shown to regulate distinct populations of H3K4me during stress response. These findings raise the interesting possibility that SAMS-1 and SAMS-4 may affect development in spr-5 and met-2 mutants that inherit increased aberrant levels of H3K4me. To test this in a curriculum-based undergraduate research experience (CURE) implemented in Developmental Biology (BIOL_4390K), students performed developmental progression assays on spr-5 and met-2 single mutants after knocking down either SAMS-1 or SAMS-4 via RNA interference (RNAi). 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.