Establishment and maintenance of heritable chromatin structure during early Drosophila embryogenesis

Abstract

During embryogenesis, the initial chromatin state is established during a period of rapid proliferative activity. We have measured with 3-min time resolution how heritable patterns of chromatin structure are initially established and maintained during the midblastula transition (MBT). We find that regions of accessibility are established sequentially, where enhancers are opened in advance of promoters and insulators. These open states are stably maintained in highly condensed mitotic chromatin to ensure faithful inheritance of prior accessibility status across cell divisions. The temporal progression of establishment is controlled by the biological timers that control the onset of the MBT. In general, acquisition of promoter accessibility is controlled by the biological timer that measures the nucleo-cytoplasmic (N:C) ratio, whereas timing of enhancer accessibility is regulated independently of the N:C ratio. These different timing classes each associate with binding sites for two transcription factors, GAGA-factor and Zelda, previously implicated in controlling chromatin accessibility at ZGA.DOI: http://dx.doi.org/10.7554/eLife.20148.001

Rapid Rates of Pol II Elongation in the Drosophila Embryo

“…This value is significantly faster than the original estimates provided by northern blotting assays using Drosophila larval tissues [5] or nuclear run-on assays using Drosophila S2 cell extracts [3]. It is possible that the “open” chromatin of pre-cellular embryos contributes to this rapid rate of elongation [12]. Moreover, many of the earlier estimates of Pol II elongation are based on the analysis of heat shock genes, and it is conceivable that the elevated temperatures needed for induction result in attenuated rates of elongation [2, 3, 6].…”

Dense Bicoid hubs accentuate binding along the morphogen gradient

“…The recent discovery of the ubiquitous factor Zelda (ZLD) and its role in the regulation of chromatin accessibility (Liang et al 2008;Harrison et al 2011;Foo et al 2014;Xu et al 2014;Schulz et al 2015;Sun et al 2015;Blythe and Wieschaus 2016) and in modulating the timing and strength of BCD-controlled (Xu et al 2014;Hannon et al 2017) and Dorsal-controlled (Foo et al 2014) enhancer activation in a concentration-dependent fashion has further strengthened the hypothesis that the interpretation of the BCD and other morphogen gradients is more complex than previously thought (Lucchetta et al 2005).…”

Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity

“…[ 46 ] Using ATAC‐seq, a handful of recent publications focusing on the early embryogenesis in D. melanogaster have explored in great detail how enhancer accessibility varies both along the temporal and spatial axes of development. [ 15,45,47,48 ] Additionally, by considering quantitative accessibility differences, they provided valuable insights into chromatin organization of different enhancer states.…”

“…The temporal dynamics of enhancer accessibility have recently been surveyed with two different experimental approaches. First, using ATAC‐seq on tightly staged individual D. melanogaster embryos, Blythe and Wieschaus [ 47 ] resolved enhancer accessibility changes to 3 min intervals. The authors demonstrated that acquisition of accessibility by enhancers, and thus their priming, preceded that of their target promoters.…”