Developmental phenotypes caused by the inappropriate inheritance of histone methylation require Polycomb Repressive Complex 2
Disciplines
Developmental Biology | Genomics
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. 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 is removed by the H3K4 demethylase, SPR-5, and H3K9me 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 severe developmental delay. Recent work from the Strome Lab shows that MES-4 repels the activity of the Polycomb Repressive Complex 2 (PRC2), which includes the H3K27 methyltransferase, MES-2, at germline gene loci in the germline. These findings prompted us to examine whether PRC2 complex-dependent H3K27me3 may contribute to the developmental delay in spr-5; met-2 mutants by concentrating ectopic H3K36me3 at germline gene loci in the soma. To test this possibility, we knocked down MES-2 using RNAi and found that the developmental delay in spr-5; met-2 mutants is completely rescued. By performing RNA-seq and ChIP-seq, we further demonstrate that knocking down MES-2 rescued the ectopic transcription of MES-4 germline genes and reduced the ectopic H3K36me3 at these loci in spr-5; met-2 mutant somas. Together, these data suggest that the PRC2 Complex contributes to a soma-to-germline transition and developmental delay in spr-5; met-2 mutants and provides mechanistic insight into how highly conserved histone modifying enzymes cooperate during development to establish germline versus somatic cell fates.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Brandon Carpenter
Developmental phenotypes caused by the inappropriate inheritance of histone methylation require Polycomb Repressive Complex 2
Histone methylation is a post-transcriptional modification to the N-terminal tails of histone core proteins that regulates DNA accessibility, and consequently, gene expression. 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 is removed by the H3K4 demethylase, SPR-5, and H3K9me 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 severe developmental delay. Recent work from the Strome Lab shows that MES-4 repels the activity of the Polycomb Repressive Complex 2 (PRC2), which includes the H3K27 methyltransferase, MES-2, at germline gene loci in the germline. These findings prompted us to examine whether PRC2 complex-dependent H3K27me3 may contribute to the developmental delay in spr-5; met-2 mutants by concentrating ectopic H3K36me3 at germline gene loci in the soma. To test this possibility, we knocked down MES-2 using RNAi and found that the developmental delay in spr-5; met-2 mutants is completely rescued. By performing RNA-seq and ChIP-seq, we further demonstrate that knocking down MES-2 rescued the ectopic transcription of MES-4 germline genes and reduced the ectopic H3K36me3 at these loci in spr-5; met-2 mutant somas. Together, these data suggest that the PRC2 Complex contributes to a soma-to-germline transition and developmental delay in spr-5; met-2 mutants and provides mechanistic insight into how highly conserved histone modifying enzymes cooperate during development to establish germline versus somatic cell fates.