SPR-5; MET-2 Maternal Reprogramming Cooperates with the Dream Complex to Regulate Developmental Cell Fates
Disciplines
Bioinformatics | Cell Biology | Developmental Biology | Genetics | Genomics | Molecular 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 the nematode, 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. Data from the Petrella and Ahringer Labs demonstrates that members of the DREAM Complex, a transcriptional repressor complex that regulates cell cycle, also represses germline genes in somatic tissues through H3K9me2 promoter marking. These data suggest that the DREAM Complex and SPR-5; MET-2 maternal reprogramming may work together to prevent ectopic expression of distinct sets of germline genes, including MES-4 germline genes, in somatic tissues and developmental delay. To test this hypothesis, we knocked down Dream Complex members LIN-35, LIN-37, LIN-52, and LIN-9 in spr-5; met-2 mutants using RNA interference (RNAi). We found that loss of each of these Dream Complex members exacerbates the severe developmental delay that we normally observe in spr-5; met-2 mutants leading to a complete L1 larval arrest. Using RNA-seq, we further demonstrate that knocking down lin-35 exacerbates the ectopic expression of MES-4 germline genes in spr-5; met-2 mutant somas. Our findings provide mechanistic insight into how evolutionary conserved transcriptional repressor complexes cooperate to ensure proper germline versus somatic cell fates during development.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Brandon Carpenter
SPR-5; MET-2 Maternal Reprogramming Cooperates with the Dream Complex to Regulate Developmental Cell Fates
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 the nematode, 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. Data from the Petrella and Ahringer Labs demonstrates that members of the DREAM Complex, a transcriptional repressor complex that regulates cell cycle, also represses germline genes in somatic tissues through H3K9me2 promoter marking. These data suggest that the DREAM Complex and SPR-5; MET-2 maternal reprogramming may work together to prevent ectopic expression of distinct sets of germline genes, including MES-4 germline genes, in somatic tissues and developmental delay. To test this hypothesis, we knocked down Dream Complex members LIN-35, LIN-37, LIN-52, and LIN-9 in spr-5; met-2 mutants using RNA interference (RNAi). We found that loss of each of these Dream Complex members exacerbates the severe developmental delay that we normally observe in spr-5; met-2 mutants leading to a complete L1 larval arrest. Using RNA-seq, we further demonstrate that knocking down lin-35 exacerbates the ectopic expression of MES-4 germline genes in spr-5; met-2 mutant somas. Our findings provide mechanistic insight into how evolutionary conserved transcriptional repressor complexes cooperate to ensure proper germline versus somatic cell fates during development.