Timing of Transcriptional Quiescence during Gametogenesis Is Controlled by Global Histone H3K4 Demethylation

• Published in: Developmental cell Vol. 23; no. 5; pp. 1059 - 1071
• Main Authors: Xu, Mengshu, Soloveychik, Maria, Ranger, Mathieu, Schertzberg, Michael, Shah, Zarna, Raisner, Ryan, Venkatasubrahmanyan, Shivkumar, Tsui, Kyle, Gebbia, Marinella, Hughes, Tim, van Bakel, Harm, Nislow, Corey, Madhani, Hiten D., Meneghini, Marc D.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 13.11.2012; Cell Press
• Subjects: animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Epigenesis, Genetic; Fundamental and applied biological sciences. Psychology; gametogenesis; Gametogenesis - genetics; Gametogenesis - physiology; Genes, Fungal; germ cells; histones; Histones - metabolism; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Meiosis; Methylation; Molecular and cellular biology; Molecular genetics; mutants; Mutation; nucleosomes; Nucleosomes - metabolism; progeny; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA, Fungal - genetics; RNA, Fungal - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; spores; Spores, Fungal - genetics; Spores, Fungal - growth & development; Spores, Fungal - metabolism; Telomere-Binding Proteins - genetics; Telomere-Binding Proteins - metabolism; Time Factors; transcription (genetics); Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; yeasts; Demethylation; Transcription; Gametogenesis; Development; Timing; Histone; Quiescence
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2012.10.005

Gametes are among the most highly specialized cells produced during development. Although gametogenesis culminates in transcriptional quiescence in plants and animals, regulatory mechanisms controlling this are unknown. Here, we confirm that gamete differentiation in the single-celled yeast Saccharomyces cerevisiae is accompanied by global transcriptional shutoff following the completion of meiosis. We show that Jhd2, a highly conserved JARID1-family histone H3K4 demethylase, activates protein-coding gene transcription in opposition to this programmed transcriptional shutoff, sustaining the period of productive transcription during spore differentiation. Moreover, using genome-wide nucleosome, H3K4me, and transcript mapping experiments, we demonstrate that JHD2 globally represses intergenic noncoding transcription during this period. The widespread transcriptional defects of JHD2 mutants are associated with precocious differentiation and the production of stress-sensitive spores, demonstrating that Jhd2 regulation of the global postmeiotic transcriptional program is critical for the production of healthy meiotic progeny. [Display omitted] ► Jhd2 globally demethylates H3K4 at intergenic regions during yeast sporulation ► JHD2 represses interfering intergenic transcription globally in postmeiotic cells ► JHD2 represses nucleosome accumulation at NDRs during sporulation ► JHD2 mutants produce prematurely formed gametes that are stress sensitive JARID histone H3K4 demethylases control a balance of differentiation versus pluripotency and drug susceptibility in normal and cancer stem cells, respectively. Xu et al. show that in budding yeast, the JARID demethylase Jhd2 is a global attenuator of noncoding transcription that sustains genic transcriptional activity and thereby delays gamete differentiation.