Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression

Abstract

SUMMARY Poised RNA polymerase II is predominantly found at developmental control genes and is thought to allow their rapid and synchronous induction in response to extracellular signals. How the recruitment of poised RNA Pol II is regulated during development is not known. By isolating muscle tissue from Drosophila embryos at five stages of differentiation, we show that the recruitment of poised Pol II occurs at many genes de novo and this makes them permissive for future gene expression. When compared to other tissues, these changes are stage-specific and not tissue-specific. In contrast, Polycomb group repression is tissue-specific and in combination with Pol II (the balanced state) marks genes with highly dynamic expression. This suggests that poised Pol II is temporally regulated and is held in check in a tissue-specific fashion. We compare our data to mammalian embryonic stem cells and discuss a framework for predicting developmental programs based on chromatin state.

RNA polymerase II pausing during development

“…This disposition for Pol II pausing among highly regulated genes is most likely due to intrinsic properties of the core promoter, as demonstrated by promoter-swapping experiments (Lagha et al, 2013) and the strong relationship between Pol II pausing and promoter sequence throughout Drosophila development (Gaertner et al, 2012;Chen et al, 2013). This suggests that transcription initiation varies between different promoter types.…”

“…In Drosophila, TATA promoters are also enriched among the earliest expressed developmental genes in the embryo but are under-represented during the main patterning stages of embryonic development. Expression of tissue-specific TATA genes only increases again towards the end of embryogenesis (Gaertner et al, 2012).…”

“…Although these promoters are typically associated with so-called housekeeping genes (which are broadly expressed across tissues, regulating such as metabolism and the cytoskeleton), they are also found at highly regulated developmental genes in mammals (Lenhard et al, 2012). The promoters are strongly nucleosome depleted and have well-positioned downstream nucleosomes with high levels of histone modifications and H2A.Z (Rach et al, 2011;Gaertner et al, 2012;Chen et al, 2013). In Drosophila, these promoters are enriched for core promoter elements such as the DNA replication-related element (DRE), and the Ohler1, Ohler6 and Ohler7 promoter motifs (Ohler et al, 2002), whereas in mammals they mostly have CpG islands.…”

Trithorax and Polycomb group-dependent regulation: a tale of opposing activities

“…Indeed, PRC1 preferentially targets paused promoters (Enderle et al, 2011). Likewise, PcG repression has been suggested to convey tissue-specific control over poised Pol II in the context of Drosophila development (Gaertner et al, 2012).…”

High‐wire act: the poised genome and cellular memory

“…What is still not completely understood is whether these two mechanisms operate independently or whether they influence each other. Genome-wide analysis has shown different levels of overlap between bivalent promoters and paused Pol II [74, 93,94]. Studies have shown the existence of two kinds of bivalent domains: one with both PRC1 and PRC2 occupancy and another with PRC2 only [95].…”