Abstract
Because chromatin determines whether information encoded in DNA is accessible to transcription factors, dynamic chromatin states in development may constrain how gene regulatory networks impart embryonic pattern. To determine the interplay between chromatin states and regulatory network function, we performed ATAC-seq on Drosophila embryos during the establishment of the segmentation network, comparing wild-type and mutant embryos in which all graded maternal patterning inputs are eliminated. While during the period between zygotic genome activation and gastrulation many regions maintain stable accessibility, cis-regulatory modules (CRMs) within the network undergo extensive patterning-dependent changes in accessibility. A component of the network, Odd-paired (opa), is necessary for pioneering accessibility of late segmentation network CRMs. opa-driven changes in accessibility are accompanied by equivalent changes in gene expression. Interfering with the timing of opa activity impacts the proper patterning of expression. These results indicate that dynamic systems for chromatin regulation directly impact the reading of embryonic patterning information.
Highlights
Embryonic patterning systems direct a set of initially uncommitted pluripotent cells to differentiate into a variety of cell types and complex tissues
We focus on the characterization of one such factor, Odd-paired (Opa), which we demonstrate is both necessary and sufficient to pioneer open chromatin states for a set of cis-regulatory modules (CRMs) critical for the function of the embryonic segmentation network
Because many of the CRMs required to generate the complex expression patterns of genes within the segmentation network are known, we used this system as a model to ask whether the zygotic genome activation (ZGA) chromatin state contains all the accessible cis-regulatory information required to complete this well-characterized developmental patterning task
Summary
Embryonic patterning systems direct a set of initially uncommitted pluripotent cells to differentiate into a variety of cell types and complex tissues. ATAC-seq measurements of chromatin accessibility in subdivided post-ZGA embryos, sampled either as posterior and anterior halves (Haines and Eisen, 2018), sorted cells purified from restricted positions along the anterior-posterior (AP) axis (Bozek et al, 2019), or as single cells (Cusanovich et al, 2018a) identify spatial heterogeneities in accessibility patterns that begin to emerge shortly after embryos undergo ZGA and initiate patterning These observations raise the question of what mechanisms drive the reshaping of the chromatin landscape following ZGA. We focus on the characterization of one such factor, Odd-paired (Opa), which we demonstrate is both necessary and sufficient to pioneer open chromatin states for a set of CRMs critical for the function of the embryonic segmentation network These results highlight that individual components of gene regulatory. Networks may operate not to activate or repress target gene expression, but to dictate how and when network components interact by controlling dynamic CRM accessibility
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