Knocking down S-adenosylmethionine synthases, SAMS-1 and SAMS-4, exacerbates developmental delay when histone methylation is inappropriately inherited
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. Maternal loss of both SPR-5 and MET-2 allows the H3K36 methyltransferase, MES-4, to maintain H3K36 methylation at germline genes in the soma leading to ectopic expression germline genes and a more severe developmental delay. Interestingly, a new study demonstrated that S-adenosylmethionine synthases, SAMS-1 and SAMS-4, which are critical enzymes in a biochemical pathway that generates the methyl donor S-adenosylmethionine (SAM), 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, met-2, and spr-5; met-2 mutants that inherit moderate and high levels of H3K4me, respectively. To test this, we are currently performing developmental progression assays on spr-5, met-2, and spr-5; met-2 mutants after knocking down either SAMS-1 or SAMS-4 via RNA interference (RNAi). We plan to present our findings at the upcoming Spring Symposium of Student Scholars.
Knocking down S-adenosylmethionine synthases, SAMS-1 and SAMS-4, exacerbates developmental delay when histone methylation is inappropriately inherited
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. Maternal loss of both SPR-5 and MET-2 allows the H3K36 methyltransferase, MES-4, to maintain H3K36 methylation at germline genes in the soma leading to ectopic expression germline genes and a more severe developmental delay. Interestingly, a new study demonstrated that S-adenosylmethionine synthases, SAMS-1 and SAMS-4, which are critical enzymes in a biochemical pathway that generates the methyl donor S-adenosylmethionine (SAM), 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, met-2, and spr-5; met-2 mutants that inherit moderate and high levels of H3K4me, respectively. To test this, we are currently performing developmental progression assays on spr-5, met-2, and spr-5; met-2 mutants after knocking down either SAMS-1 or SAMS-4 via RNA interference (RNAi). We plan to present our findings at the upcoming Spring Symposium of Student Scholars.