A global change in RNA polymerase II pausing during the Drosophila midblastula transition

Abstract

Massive zygotic transcription begins in many organisms during the midblastula transition when the cell cycle of the dividing egg slows down. A few genes are transcribed before this stage but how this differential activation is accomplished is still an open question. We have performed ChIP-seq experiments on tightly staged Drosophila embryos and show that massive recruitment of RNA polymerase II (Pol II) with widespread pausing occurs de novo during the midblastula transition. However, ∼100 genes are strongly occupied by Pol II before this timepoint and most of them do not show Pol II pausing, consistent with a requirement for rapid transcription during the fast nuclear cycles. This global change in Pol II pausing correlates with distinct core promoter elements and associates a TATA-enriched promoter with the rapid early transcription. This suggests that promoters are differentially used during the zygotic genome activation, presumably because they have distinct dynamic properties.DOI: http://dx.doi.org/10.7554/eLife.00861.001

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.…”

“…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.…”

New insights into the maternal to zygotic transition

“…The MZT represents an extreme scenario of these processes and therefore, by studying this event, we will continue to improve our knowledge of transcription and cell cycle behaviour. For example, although the chromatin modification marks H3K4me3 and H3K27me3 associate with transcriptionally active and repressed zygotic genes, respectively, they play no role in transcriptional regulation prior to the MBT (Barski et al, 2007;Vastenhouw et al, 2010;Chen et al, 2013). How can we begin to uncover the mechanisms regulating the events of the MZT?…”

“…However, even though this threshold has been achieved, transcription does not initiate until the MBT because genomic DNA is held in a state that is incompatible with transcription. methylation (H3K27me3), which are normally associated with transcriptionally active and repressed genes, respectively, are unlikely to play a role: these marks do not appear in the zebrafish or Drosophila embryo until the time of zygotic transcription initiation (Barski et al, 2007;Vastenhouw et al, 2010;Chen et al, 2013). Although these specific marks might therefore regulate the zygotic expression of particular genes, they are unlikely to act as global regulators of transcriptional quiescence prior to zygotic transcription initiation or to global activation of transcription thereafter.…”

Modulation of temporal dynamics of gene transcription by activator potency in theDrosophilaembryo

“…To further evaluate the specificity of the effect of the Bcd mutation, we analyzed active hb transcription at a location (PS4) known to be independent of Bcd as a direct input (Perry et al, 2012;Chen et al, 2013). The intron dot number at PS4 (ρ PS4 ) exhibits similar profiles in wt and mutant embryos at nc14 ( Fig.…”