Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells

• Published in: G3 : genes - genomes - genetics Vol. 4; no. 1; pp. 143 - 153
• Main Authors: Tabuchi, Tomoko M, Rechtsteiner, Andreas, Strome, Susan, Hagstrom, Kirsten A
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 10-01-2014
• Subjects: Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Gene Expression Regulation, Developmental; Germ Cells - metabolism; Investigations; Microarray Analysis; Trans-Activators - genetics; Trans-Activators - metabolism; X Chromosome - genetics; X Chromosome - metabolism; development; chromatin; gene regulation; germ cells; X chromosome
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1534/g3.113.007849

During animal development, gene transcription is tuned to tissue-appropriate levels. Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 (Maternal Effect Sterile-4) marks genes expressed in the germline with methylated lysine on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosome. The DRM transcription factor complex, named for its Dp/E2F, Retinoblastoma-like, and MuvB subunits, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 and the DRM subunit lin-54 oppositely skew the transcript levels of their common targets and cause sterility. A double mutant restores target gene transcript levels closer to wild type, and the concomitant loss of lin-54 suppresses the severe germline proliferation defect observed in mes-4 single mutants. Together, "yin-yang" regulation by MES-4 and DRM ensures transcript levels appropriate for germ-cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.