The Polycomb Complex 2 contributes to developmental delay when histone methylation is inappropriately inherited
type: CreativeWork
description: 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 is removed by the H3K4 demethylase, SPR-5, and H3K9me is subsequently added by the histone methyltransferase, MET-2. Recently, it was demonstrated that SPR- 5 and 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-marked germline genes in somatic tissues and a severe developmental delay. Work from the Strome Lab showed that the Polycomb Repressive Complex II (PRC2), which includes the H3K27 methyltransferase, MES-2, antagonizes MES-4 activity to maintain proper gene expression during early embryogenesis. This data hints that in the absence of SPR-5 and MET-2 maternal reprogramming, MES-2 may prevent a more severe developmental delay by antagonizing MES-4. To test this hypothesis, we knocked down MES-2 maternally and found that the developmental delay in spr-5; met-2 mutants is completely rescued. This exciting result suggests that H3K27me contributes to MES-4 germline gene misexpression in the somatic tissues of spr-5; met-2 mutants. We completed RNA-seq, ChIP-seq and qRT-PCR experiments to further examine how these histone modifying enzymes cooperate to regulate proper germline versus somatic gene expression. We also observed that the developmental delay phenotype in spr-5; met-2 mutants can be rescued by knocking down MES-2 after embryogenesis. Our work provides mechanistic insight into…
abstract: 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 is removed by the H3K4 demethylase, SPR-5, and H3K9me is subsequently added by the histone methyltransferase, MET-2. Recently, it was demonstrated that SPR- 5 and 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-marked germline genes in somatic tissues and a severe developmental delay. Work from the Strome Lab showed that the Polycomb Repressive Complex II (PRC2), which includes the H3K27 methyltransferase, MES-2, antagonizes MES-4 activity to maintain proper gene expression during early embryogenesis. This data hints that in the absence of SPR-5 and MET-2 maternal reprogramming, MES-2 may prevent a more severe developmental delay by antagonizing MES-4. To test this hypothesis, we knocked down MES-2 maternally and found that the developmental delay in spr-5; met-2 mutants is completely rescued. This exciting result suggests that H3K27me contributes to MES-4 germline gene misexpression in the somatic tissues of spr-5; met-2 mutants. We completed RNA-seq, ChIP-seq and qRT-PCR experiments to further examine how these histone modifying enzymes cooperate to regulate proper germline versus somatic gene expression. We also observed that the developmental delay phenotype in spr-5; met-2 mutants can be rescued by knocking down MES-2 after embryogenesis. Our work provides mechanistic insight into…
author: Morgan- Benitez, Sydney
keywords: Polycomb Repressor Complex 2, Caenorhabditis elegans, Maternal reprogramming, Histone methylation, SPR-5, MET-2, Biology, Integrative Biology
date published: 2023-06-14T07:00:00Z
date modified: 2026-07-24T02:44:06Z
provider: Kennesaw State University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Kennesaw State University