Sequential changes at differentiation gene promoters as they become active in a stem cell lineage

Citations Over TimeTop 10% of 2011 papers

Abstract

Transcriptional silencing of terminal differentiation genes by the Polycomb group (PcG) machinery is emerging as a key feature of precursor cells in stem cell lineages. How, then, is this epigenetic silencing reversed for proper cellular differentiation? Here, we investigate how the developmental program reverses local PcG action to allow expression of terminal differentiation genes in the Drosophila male germline stem cell (GSC) lineage. We find that the silenced state, set up in precursor cells, is relieved through developmentally regulated sequential events at promoters once cells commit to spermatocyte differentiation. The programmed events include global downregulation of Polycomb repressive complex 2 (PRC2) components, recruitment of hypophosphorylated RNA polymerase II (Pol II) to promoters, as well as the expression and action of testis-specific homologs of TATA-binding protein-associated factors (tTAFs). In addition, action of the testis-specific meiotic arrest complex (tMAC), a tissue-specific version of the MIP/dREAM complex, is required both for recruitment of tTAFs to target differentiation genes and for proper cell type-specific localization of PRC1 components and tTAFs within the spermatocyte nucleolus. Together, the action of the tMAC and tTAF cell type-specific chromatin and transcription machinery leads to loss of Polycomb and release of stalled Pol II from the terminal differentiation gene promoters, allowing robust transcription.

Related Papers

• → Trithorax and Polycomb group-dependent regulation: a tale of opposing activities(2015)151 cited
• → The multiscale effects of polycomb mechanisms on 3D chromatin folding(2019)44 cited
• → MicroRNAs of the miR-290–295 Family Maintain Bivalency in Mouse Embryonic Stem Cells(2016)26 cited
• → The Proportion of Chromatin Graded between Closed and Open States Determines the Level of Transcripts Derived from Distinct Promoters in the CYP19 Gene(2015)7 cited
• → Genomic targeting and function of polycomb repressive complex 2 and ISWI chromatin remodelers(2017)