Cohesin facilitates zygotic genome activation in zebrafish

Abstract

At zygotic genome activation (ZGA), changes in chromatin structure are associated with new transcription immediately following the maternal-to-zygotic transition (MZT). The nuclear architectural proteins cohesin and CCCTC-binding factor (CTCF) contribute to chromatin structure and gene regulation. We show here that normal cohesin function is important for ZGA in zebrafish. Depletion of the cohesin subunit Rad21 delays ZGA without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA, whereas complete abrogation is lethal. Genome-wide analysis of Rad21 binding reveals a change in distribution from pericentromeric satellite DNA and other locations, including the locus (the products of which are responsible for maternal transcript degradation), to genes, as embryos progress through the MZT. After MZT, a subset of Rad21 binding overlaps the pioneer factor Pou5f3, which activates early expressed genes. Rad21 depletion disrupts the formation of nucleoli and RNA polymerase II foci, suggestive of global defects in chromosome architecture. We propose that Rad21/cohesin redistribution to active areas of the genome is key to the establishment of chromosome organization and the embryonic developmental program.

Pou5f3, SoxB1 and Nanog remodel chromatin on High Nucleosome Affinity Regions at Zygotic Genome Activation

“…We compared our data with recently published ATAC-seq based chromatin accessibility data . Weak ATAC-seq signals which did not meet the standard cutoffs in Liu et al 2018 andMeier et al 2018 were detectable when aligned on all TFBS (Fig. 1D).…”

Condensins and cohesins – one of these things is not like the other!

“…A key stage in development is the transition from the maternal to zygotic control of transcription (also termed zygotic genome activation; ZGA). Embryos with reduced levels of cohesin (RAD21) retain elevated levels of maternal mRNAs, suggesting that cohesin is critical for maternal mRNA turnover and subsequent expression of zygotic mRNAs (Rosa and Brivanlou, 2017;Meier et al, 2018). In embryos that contain wild-type levels of cohesin, ChIP-seq revealed an extensive increase in the number of cohesin-decorated DNA sites post-ZGAespecially at enhancers and/or promoters that carry histone modifications indicative of activated genes (Bogdanovic et al, 2012;Meier et al, 2018).…”

“…Embryos with reduced levels of cohesin (RAD21) retain elevated levels of maternal mRNAs, suggesting that cohesin is critical for maternal mRNA turnover and subsequent expression of zygotic mRNAs (Rosa and Brivanlou, 2017;Meier et al, 2018). In embryos that contain wild-type levels of cohesin, ChIP-seq revealed an extensive increase in the number of cohesin-decorated DNA sites post-ZGAespecially at enhancers and/or promoters that carry histone modifications indicative of activated genes (Bogdanovic et al, 2012;Meier et al, 2018). If cohesins regulate transcription on a gene-by-gene basis, one would expect that those genes identified through altered mRNA levels would be the same genes that exhibit cohesin-binding to their enhancers and/or promoters.…”

MET-2, a SETDB1 family methyltransferase, coordinates embryo events through distinct histone H3 methylation states

“…The nature of the relationship between zygotic transcription and chromatin regulation has been uncertain. Chromatin regulation could precede and initiate zygotic transcription (Meier et al, 2018;Østrup et al, 2013). Conversely, zygotic transcription may help shape chromatin structure, a model that has been tested by several studies: A study that analyzed the spatial genome organization in fly embryos revealed that early expressed genes correlate with the boundaries of Topologically Associating Domains (TADs).…”