Histone methyltransferases, SET-2 and MES-4, contribute to sterility in C. elegans that inappropriately inherit histone methylation
Disciplines
Life Sciences
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. Maternal loss of SPR-5 and MET-2 results in inherited phenotypes such as developmental delay and sterility in the progeny. We recently demonstrated that knocking down the H3K36 methyltransferase, MES-4, which maintains a transcriptional memory of germline genes between generations, or the H3K4me1/2 methyltransferase, SET-2, a member of the COMPASS complex rescues developmental delay in spr-5; met-2 mutant progeny. However, whether knocking down MES-4 or SET-2 rescues sterility in spr-5; met-2 double mutants has yet to be explored. Here, we test this possibility by feeding spr-5; met-2 mutant hermaphrodites either set-2 or mes-4 RNAi and examining germlines of their synchronized progeny at the young adult stage using DIC microscopy, DAPI staining, and by quantifying the total number of oocytes across both gonad arms. Excitingly, we find that knocking down either SET-2 or MES-4 significantly rescues germline health in spr-5; met-2 progeny, with some spr-5; met-2 progeny germlines from hermaphrodites fed set-2 RNAi containing viable embryos. Together, our data suggest that the inherited sterility in the absence of SPR-5 and MET-2 maternal reprograming may be caused by inherited H3K4 methylation and altered germline transcription. While the mechanisms underlying sterility in spr-5; met-2 mutants remain to be determined, our results provide further evidence that C. elegans utilizes a combination of inherited histone modifications to achieve the correct levels of transcription to properly specify tissues. This project is supported by NIH R15 1R15GM148887-01A1 (PI: Carpenter) and NIH U-RISE 1T34GM140948-01A1 (PIs: Hudson and Griffin).
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. Maternal loss of SPR-5 and MET-2 results in inherited phenotypes such as developmental delay and sterility in the progeny. We recently demonstrated that knocking down the H3K36 methyltransferase, MES-4, which maintains a transcriptional memory of germline genes between generations, or the H3K4me1/2 methyltransferase, SET-2, a member of the COMPASS complex rescues developmental delay in spr-5; met-2 mutant progeny. However, whether knocking down MES-4 or SET-2 rescues sterility in spr-5; met-2 double mutants has yet to be explored. Here, we test this possibility by feeding spr-5; met-2 mutant hermaphrodites either set-2 or mes-4 RNAi and examining germlines of their synchronized progeny at the young adult stage using DIC microscopy, DAPI staining, and by quantifying the total number of oocytes across both gonad arms. Excitingly, we find that knocking down either SET-2 or MES-4 significantly rescues germline health in spr-5; met-2 progeny, with some spr-5; met-2 progeny germlines from hermaphrodites fed set-2 RNAi containing viable embryos. Together, our data suggest that the inherited sterility in the absence of SPR-5 and MET-2 maternal reprograming may be caused by inherited H3K4 methylation and altered germline transcription. While the mechanisms underlying sterility in spr-5; met-2 mutants remain to be determined, our results provide further evidence that C. elegans utilizes a combination of inherited histone modifications to achieve the correct levels of transcription to properly specify tissues. This project is supported by NIH R15 1R15GM148887-01A1 (PI: Carpenter) and NIH U-RISE 1T34GM140948-01A1 (PIs: Hudson and Griffin).