Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.
Zygotic genome activation (ZGA) initiates regionalized transcription responsible for the acquisition of distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, whether the tissue-specific transcription is mechanistically linked with the onset of ZGA is unknown. Here, we have addressed the involvement of chromatin organizer SATB2 in orchestrating these processes during vertebrate embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility revealed contrasting molecular functions of maternal and zygotic pools of Satb2. Maternal Satb2 represses zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented. We discuss the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.
The long non-coding RNA XIST is the master regulator for the process of X chromosome inactivation (XCI) in mammalian females. Here we report the existence of a hitherto uncharacterized
cis
regulatory element (cRE) within the first exon of human
XIST
, which determines the transcriptional status of
XIST
during the initiation and maintenance phases of XCI. In the initiation phase, pluripotency factors bind to this cRE and keep
XIST
repressed. In the maintenance phase of XCI, the cRE is enriched for CTCF which activates
XIST
transcription. By employing a CRISPR-dCas9-KRAB based interference strategy, we demonstrate that binding of CTCF to the newly identified cRE is critical for regulating
XIST
in a YY1-dependent manner. Collectively, our study uncovers the combinatorial effect of multiple transcriptional regulators influencing
XIST
expression during the initiation and maintenance phases of XCI.
The long non-coding RNA XIST is the master regulator for the process of X chromosome inactivation in mammalian females. Here we report the existence of a hitherto uncharacterized cis regulatory element within the first exon of human XIST, which by associating with the promoter region through chromatin looping defines the transcriptional status of XIST. This interaction is brought about by CTCF, which in turn assists towards the maintenance of YY1 binding at the promoter and governs XIST transcription. Strikingly, the cis element is competitively bound by pluripotency factors and CTCF, wherein the enrichment of the former disrupts its interaction with thepromoter, leading to downregulation of XIST. Based on sequence similarity of this element across species we propose that this mechanism is conserved between the human and mouse systems. Collectively, our study uncovers the
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