A Major Regulator of Germline Transcription, LSL-1, Contributes to Developmental Defects when Histone Methylation is Inappropriately Inherited
Disciplines
Biology | Cell and Developmental Biology
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. Maternal loss of SPR-5 and MET-2 results in ectopic expression of germline genes in somatic tissues and a range of developmental phenotypes, including a severe developmental delay. Using a combination of RNA-seq and ChIP-seq experiments, a recent study identified a major regulator of germline transcription, LSL-1, that binds and turns on germline genes in the germline during development. From our own transcriptional analysis performed on C. elegans lacking SPR-5 and MET-2, we find that lsl-1 is significantly upregulated in somatic tissues. Together these data suggest that LSL-1 may be turning on germline genes aberrantly in somatic tissue and contributing to developmental delay. To test this hypothesis, we knocked down lsl-1 using RNA interference (RNAi) and found that the developmental delay in spr-5; met-2 mutants is significantly rescued. Using RNA-seq, we further demonstrate that knocking down LSL-1 in spr-5; met-2 mutant rescues ectopic expression of MES-4 germline genes. Together, our findings provide mechanistic insight into how inappropriate inheritance of epigenetic states perturb germline versus somatic cell fates specification during development and how this perturbation contributes to developmental phenotypes.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Brandon Carpenter
A Major Regulator of Germline Transcription, LSL-1, Contributes to Developmental Defects when Histone Methylation is Inappropriately Inherited
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. Maternal loss of SPR-5 and MET-2 results in ectopic expression of germline genes in somatic tissues and a range of developmental phenotypes, including a severe developmental delay. Using a combination of RNA-seq and ChIP-seq experiments, a recent study identified a major regulator of germline transcription, LSL-1, that binds and turns on germline genes in the germline during development. From our own transcriptional analysis performed on C. elegans lacking SPR-5 and MET-2, we find that lsl-1 is significantly upregulated in somatic tissues. Together these data suggest that LSL-1 may be turning on germline genes aberrantly in somatic tissue and contributing to developmental delay. To test this hypothesis, we knocked down lsl-1 using RNA interference (RNAi) and found that the developmental delay in spr-5; met-2 mutants is significantly rescued. Using RNA-seq, we further demonstrate that knocking down LSL-1 in spr-5; met-2 mutant rescues ectopic expression of MES-4 germline genes. Together, our findings provide mechanistic insight into how inappropriate inheritance of epigenetic states perturb germline versus somatic cell fates specification during development and how this perturbation contributes to developmental phenotypes.