Histone methyltransferases, SET-2 and MES-4, contribute to sterility in C. elegans that inappropriately inherit histone methylation
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 H3K36 methyltransferase, MES-4, which maintains a transcriptional memory of a subset of germline genes between generations, and H3K4me3 methyltransferase, SET-2, a member of the COMPASS complex. Maternal loss of SPR-5 and MET-2 results in ectopic expression of MES-4 germline genes and overexpression of H3K4 methylation. Together, this leads to developmental delay and sterility. We recently demonstrated that knocking down mes-4 and set-2 rescues the somatic developmental delay. However, whether knocking down mes-4 and set-2 rescues sterility in spr-5; met-2 double mutants has yet to be explored. To examine whether knocking down mes-4 and set-2 rescues sterility in spr-5; met-2 mutants, we knocked down mes-4 and set-2 using RNAi then performed DAPI staining and DIC imaging of the germlines. Excitingly, we found that knocking down mes-4 and set-2 significantly increases the number of oocytes in spr-5; met-2 mutants. These data demonstrate that ectopic H3K4me and H3K36me contribute to sterility in the absence of SPR-5; MET-2 maternal reprogramming. Our findings provide mechanistic insight into how evolutionary conserved histone methylation and maternal reprogramming ensure development of a germline.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Brandon Carpenter
Histone methyltransferases, SET-2 and MES-4, contribute to sterility in C. elegans that inappropriately inherit histone methylation
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 H3K36 methyltransferase, MES-4, which maintains a transcriptional memory of a subset of germline genes between generations, and H3K4me3 methyltransferase, SET-2, a member of the COMPASS complex. Maternal loss of SPR-5 and MET-2 results in ectopic expression of MES-4 germline genes and overexpression of H3K4 methylation. Together, this leads to developmental delay and sterility. We recently demonstrated that knocking down mes-4 and set-2 rescues the somatic developmental delay. However, whether knocking down mes-4 and set-2 rescues sterility in spr-5; met-2 double mutants has yet to be explored. To examine whether knocking down mes-4 and set-2 rescues sterility in spr-5; met-2 mutants, we knocked down mes-4 and set-2 using RNAi then performed DAPI staining and DIC imaging of the germlines. Excitingly, we found that knocking down mes-4 and set-2 significantly increases the number of oocytes in spr-5; met-2 mutants. These data demonstrate that ectopic H3K4me and H3K36me contribute to sterility in the absence of SPR-5; MET-2 maternal reprogramming. Our findings provide mechanistic insight into how evolutionary conserved histone methylation and maternal reprogramming ensure development of a germline.