Maternal H3K36 and H3K27 HMTs Protect Germline Development Via Regulation of the Transcription Factor LIN-15B

Overview

Journal Elife

Specialty Biology

Date 2022 Aug 3

PMID 35920536

Authors

Chad Steven Cockrum

Susan Strome

Affiliations

Soon will be listed here.

Abstract

Maternally synthesized products play critical roles in the development of offspring. A premier example is the H3K36 methyltransferase MES-4, which is essential for germline survival and development in offspring. How maternal MES-4 protects the germline 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 nascent germlines (PGCs and their descendants) dissected from wild-type and mutant (lacking maternal and zygotic MES-4) larvae. nascent germlines displayed downregulation of some germline genes, upregulation of some somatic genes, and dramatic upregulation of hundreds of genes on the X chromosome. We demonstrated that upregulation of one or more genes on the X is the cause of germline death by generating and analyzing mutants that inherited different endowments of X chromosome(s). Intriguingly, removal of the THAP transcription factor LIN-15B from mutants reduced X misexpression and prevented germline death. is X-linked and misexpressed in PGCs, identifying it as a critical target for MES-4 repression. The above findings extend to the H3K27 methyltransferase MES-2/3/6, the 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.

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