Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Abstract

In many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hyper-transcribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription.Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

Nanog safeguards early embryogenesis against global activation of maternal β-catenin activity by interfering with TCF factors

“…Through a series of genetic and biochemical studies, we uncovered a novel repressor of maternal β-catenin activity, Nanog, which suppresses the transcriptional activity of Wnt/β-catenin signaling by competitive binding to transcription-activator type Tcf7 and disrupting the functional β-catenin/TCF complex. Our study therefore establishes the maternal Nanog, which has shown to play a central role in MZT [ 47 , 48 ] as a key factor that safeguards the embryo against global activation of maternal β-catenin activity.…”

“…In view of the key role of Nanog in activating the first wave of zygotic genes and clearance of maternal mRNA [47,48], our study further establishes a central role of Nanog in coordinating early embryonic development of zebrafish.…”

“…(E) Relative β-catenin transcriptional activity in embryos of WT, MZnanog, and MZnanog injected with tcf7)_ΔβBD, tcf7_ΔHMG, or ctnnbip1 mRNA at 4 hpf examined by TOPflash assay. Error bars, mean ± SD, � P < 0.05, study therefore establishes the maternal Nanog, which has shown to play a central role in MZT [47,48] as a key factor that safeguards the embryo against global activation of maternal β-catenin activity.…”

“…In previous studies, maternal Nanog has shown to play a key role in controlling MZT, mainly including ZGA and the clearance of maternal mRNA, together with Pou5f1 and SoxB1 [ 47 , 48 ]. In our study, we generate MZ nanog mutants and show that the transcriptional activation of a series of zygotic genes is defective, and the clearance of maternal transcripts is strongly disrupted in MZ nanog embryos, strongly supporting the critical role of Nanog in mediating MZT.…”

“…Although Nanog is not on the list of the classical Yamanaka factors for induced pluripotent stem (iPS) cells, it has been demonstrated to be a "master switch" in the acquisition of cell pluripotency [ 45 ]. In zebrafish, previous studies have shown that nanog is a pivotal maternal factor to mediate endoderm formation through the Mxtx2-Nodal signaling in the extraembryonic yolk syncytial layer [ 46 ], and to initiate the zygotic genome activation (ZGA) together with Pou5f3 and SoxB1 during maternal zygotic transition (MZT) [ 47 , 48 ]. Recently, by generating maternal -zygotic mutants of nanog (MZ nanog ), 2 studies further proved that zebrafish nanog is primarily required for extraembryonic development [ 49 ], and it is crucial for embryonic architecture formation and cell survival [ 50 ].…”