Zygotic modulation of inappropriate inherited histone methylation partially rescues developmental phenotypes
Disciplines
Bioinformatics | Cell Biology | Developmental Biology | Genetics
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, it was 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 severe developmental delay. Recent studies in our lab have demonstrated that knocking down components of the Polycomb Repressive Complex II (PRC2) completely rescues spr-5; met-2 developmental delay, whereas knocking down members of the DREAM complex exacerbates the developmental delay in spr-5; met-2 mutants. These exciting findings suggest that different chromatin complexes can either synergize with, or antagonize, SPR-5; MET-2 maternal reprogramming. For these experiments we knocked down components of the PRC2 and DREAM complexes maternally in spr-5; met-2 mutants. Here, we are investigating the potential modulation the PRC2 and DREAM complexes further downstream, focusing on the loss in the zygote rather at the maternal level. To do this, we knocked down MES-2 (PRC2 complex member) and LIN-35 (DREAM complex member) in L1 larvae by RNAi and found that the developmental delay in spr-5; met-2 mutants is partially rescued. This data hints that in the absence of SPR-5; MET-2 maternal reprogramming, targeting different chromatin complexes may provide a way to alleviate some of the severe developmental phenotypes that arise when histone methylation is inappropriately inherited.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Brandon Carpenter
Zygotic modulation of inappropriate inherited histone methylation partially rescues developmental phenotypes
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, it was 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 severe developmental delay. Recent studies in our lab have demonstrated that knocking down components of the Polycomb Repressive Complex II (PRC2) completely rescues spr-5; met-2 developmental delay, whereas knocking down members of the DREAM complex exacerbates the developmental delay in spr-5; met-2 mutants. These exciting findings suggest that different chromatin complexes can either synergize with, or antagonize, SPR-5; MET-2 maternal reprogramming. For these experiments we knocked down components of the PRC2 and DREAM complexes maternally in spr-5; met-2 mutants. Here, we are investigating the potential modulation the PRC2 and DREAM complexes further downstream, focusing on the loss in the zygote rather at the maternal level. To do this, we knocked down MES-2 (PRC2 complex member) and LIN-35 (DREAM complex member) in L1 larvae by RNAi and found that the developmental delay in spr-5; met-2 mutants is partially rescued. This data hints that in the absence of SPR-5; MET-2 maternal reprogramming, targeting different chromatin complexes may provide a way to alleviate some of the severe developmental phenotypes that arise when histone methylation is inappropriately inherited.