Maternal H3K36 and H3K27 HMTs protect germline immortality via regulation of the transcription factor LIN-15B

Abstract

Maternally synthesized products play critical roles in development of offspring. A premier example is the C. elegans H3K36 methyltransferase MES-4, which is essential for germline survival and development in offspring. How maternal MES-4 protects germline immortality is not well understood, but its role in H3K36 methylation hinted that it may regulate gene expression in Primordial Germ Cells (PGCs). We tested this hypothesis by profiling transcripts from single pairs of PGCs dissected from wild-type and mes-4 mutant (lacking maternal and zygotic MES-4) newly hatched larvae. We found that mes-4 PGCs display normal turn-on of most germline genes and normal repression of somatic genes, but dramatically up-regulate hundreds of genes on the X chromosome. We demonstrated that X mis-expression is the cause of germline death by generating and analyzing mes-4 mutants that inherited different endowments of X chromosome(s). Intriguingly, removal of the THAP transcription factor LIN-15B from mes-4 mutants reduced X mis-expression and prevented germline death. lin-15B is X-linked and mis-expressed in mes-4 PGCs, identifying it as a critical target for MES-4 repression. The above findings extend to the H3K27 methyltransferase MES-2/3/6, the C. elegans version of Polycomb Repressive Complex 2. We propose that maternal MES-4 and PRC2 cooperate to protect germline survival by preventing synthesis of germline-toxic products encoded by genes on the X chromosome, including the key transcription factor LIN-15B.

Maternal H3K36 and H3K27 HMTs protect germline development via regulation of the transcription factor LIN-15B

“…Newly created materials and protocols are available upon request. Custom scripts used to process and analyze data are available in the following GitHub repository: https://github.com/ccockrum-ucsc/mes-transcriptomics , (copy archived at swh:1:rev:20c99ad1168e8b8705004dd4e979bf39a5443f60 , Cockrum and Strome, 2022 ). Supplementary file 1 contains differentially expressed genes for all comparisons we analyzed.…”