RESUMO
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.
Assuntos
Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Fatores de Transcrição/metabolismo , Vertebrados/embriologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Animais , Cromatina/genética , Cromatina/metabolismo , Desenvolvimento Embrionário , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/genética , Fatores de Transcrição/genética , Transcriptoma , Vertebrados/genética , Vertebrados/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Zigoto/metabolismoRESUMO
Neguembor et al. (2021) use super-resolution microscopy to illuminate genome packaging inside the cell nucleus. They discover that transcription and topoisomerases protect chromatin from collapsing in a crumpled state refractory to DNA loop extrusion by cohesin proteins.
Assuntos
Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Proteínas de Ciclo Celular/genética , Cromatina/genética , Proteínas Cromossômicas não Histona/genética , DNA/genética , Humanos , CoesinasRESUMO
The long noncoding 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.
