The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation

Hadzhiev, Yavor; Wheatley, Lucy; Cooper, Ledean; Ansaloni, Federico; Whalley, Celina M.; Chen, Zhelin; Gustincich, Stefano; Sanges, Remo; Burgess, Shawn M.; Beggs, Andrew D; Mueller, Ferenc

doi:10.1101/2021.08.09.455629

Cited by 2 publications

(2 citation statements)

References 98 publications

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“…Transcription bodies have been observed in multiple systems (Cisse et al 2013; Boehning et al 2018; Cho et al 2018; Ghamari et al 2013; Iborra et al 1996; Jackson et al 1998; Huang et al 2021; Hadzhiev et al 2021). It is unclear, however, what organizes their formation.…”

Section: Transcription Factors Cluster Prior To and Independent Of Tr...mentioning

confidence: 99%

“…Transcription by RNA polymerase II (RNA Pol II) takes place in concentrated areas in the nucleus, also called transcription bodies (Cisse et al 2013; Boehning et al 2018; Cho et al 2018; Ghamari et al 2013; Iborra et al 1996; Jackson et al 1998; Huang et al 2021; Hadzhiev et al 2021). Recently, it has been shown that clusters of RNA Pol II and Mediator localize to such transcription bodies (Cho et al 2018).…”

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confidence: 99%

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Nanog organizes transcription bodies

Kuznetsova

Ugolini

et al. 2022

Preprint

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The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. How proteins of the transcriptional machinery come together to form such bodies, however, is unclear. Here, we take advantage of two large, isolated, and long-lived transcription bodies that reproducibly form during early zebrafish embryogenesis, to characterize the dynamics of transcription body formation. Once formed, these transcription bodies are enriched for initiating and elongating RNA polymerase II, as well as the transcription factors Nanog and Sox19b. Analyzing the events leading up to transcription, we find that Nanog and Sox19b cluster prior to transcription, and independently of RNA accumulation. The clustering of transcription factors is sequential; Nanog clusters first, and this is required for the clustering of Sox19b and the initiation of transcription. Mutant analysis revealed that both the DNA-binding domain, as well as one of the two intrinsically disordered regions of Nanog are required to organize the two bodies of transcriptional activity. Taken together, our data suggests that the clustering of transcription factors dictates the formation of transcription bodies.

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Section: Transcription Factors Cluster Prior To and Independent Of Tr...mentioning

confidence: 99%

mentioning

confidence: 99%

Nanog organizes transcription bodies

Kuznetsova

Ugolini

et al. 2022

Preprint

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Transposable elements drive the evolution of metazoan zinc finger genes

Wells

Chang

McCormick

et al. 2022

Preprint

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Cys2-His2 Zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by the rapid expansion and contraction of numerous subfamilies across the animal phylogeny. The forces and mechanisms underlying rapid ZNF evolution remain poorly understood, but there is growing evidence that the targeting and repression of lineage-specific transposable elements (TEs) plays a major role in the diversification of the Kruppel-associated box ZNF (KZNF) subfamily, which predominates in tetrapod genomes. At present, it is unknown whether this function and co-evolutionary relationship is unique to KZNFs, or a broader feature of metazoan ZNFs. Here, we present evidence that genomic conflict with TEs has been a central driver in the diversification of ZNFs in animals. Sampling from more than 4000 animal genome assemblies, we show that the copy number of retroelements correlates with that of ZNFs across at least 750 million years of metazoan evolution, both within and between major taxonomic groups. Using computational predictions, we show that ZNFs preferentially bind TEs in a diverse set of representative animal species. We further investigate one of the most expansive ZNF subfamilies found in cyprinid fish, which are characterized by a conserved domain we dubbed theFishN-terminalZinc-finger associated (FiNZ) domain. FiNZ-ZNFs have dramatically expanded in several fish species, including the zebrafish in which we predict ~700 FiNZ-ZNF genes. Almost all are located on the long arm of chromosome 4, and recent duplicates are evolving adaptively under positive selection. Like mammalian KZNFs, the bulk of zebrafish FiNZ-ZNFs are expressed in waves at the onset of zygotic genome activation. Blocking FiNZ-ZNF translation using morpholinos during early zebrafish embryogenesis results in a global de-repression of young, transcriptionally active TEs, likely driven by the failure to establish heterochromatin over these elements. Together, these data suggest that ZNF diversification has been intimately connected to TE expansion throughout animal evolution and that families of ZNFs have been deployed independently in fish and mammals to repress TEs during early embryogenesis.

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The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation

Cited by 2 publications

References 98 publications

Nanog organizes transcription bodies

Nanog organizes transcription bodies

Transposable elements drive the evolution of metazoan zinc finger genes

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