SPR-5 and MET-2 Maternal Reprogramming Cooperates with DREAM and MEC Complexes to Regulate Developmental Cell Fates
Disciplines
Cell Biology | Developmental Biology
Abstract (300 words maximum)
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 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; 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. Furthermore, preliminary data from our lab shows that the histone deacetylation, MEC Complex, is also required to prevent a soma-to-germline transition. These data suggest that the DREAM complex, MEC complex, and SPR-5; MET-2 maternal reprogramming work together to prevent ectopic expression of germline genes in somatic tissues and developmental delay. To test this hypothesis, we knocked down Dream complex and MEC complex members in spr-5; met-2 mutants using RNAi and found that knocking down either complex exacerbates the severe developmental delay that we normally observe in spr-5; met-2. Using RNA-seq, we further demonstrate that knocking down Dream and MEC complex members 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 and reprogramming of histone methylation synergize 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 and MET-2 Maternal Reprogramming Cooperates with DREAM and MEC Complexes to Regulate Developmental Cell Fates
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 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; 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. Furthermore, preliminary data from our lab shows that the histone deacetylation, MEC Complex, is also required to prevent a soma-to-germline transition. These data suggest that the DREAM complex, MEC complex, and SPR-5; MET-2 maternal reprogramming work together to prevent ectopic expression of germline genes in somatic tissues and developmental delay. To test this hypothesis, we knocked down Dream complex and MEC complex members in spr-5; met-2 mutants using RNAi and found that knocking down either complex exacerbates the severe developmental delay that we normally observe in spr-5; met-2. Using RNA-seq, we further demonstrate that knocking down Dream and MEC complex members 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 and reprogramming of histone methylation synergize to ensure proper germline versus somatic cell fates during development.