The miR-430 locus with extreme promoter density forms a transcription body during the minor wave of zygotic genome activation

Yavor Hadzhiev, Lucy Wheatley, Ledean Cooper, Federico Ansaloni, Celina Whalley, Zhelin Chen, Sara Finaurini, Stefano Gustincich, Remo Sanges, Shawn Burgess, Andrew Beggs, Ferenc Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

In anamniote embryos, the major wave of zygotic genome activation starts during the mid-blastula transition. However, some genes escape global genome repression, are activated substantially earlier, and contribute to the minor wave of genome activation. The mechanisms underlying the minor wave of genome activation are little understood. We explored the genomic organization and cis-regulatory mechanisms of a transcription body, in which the minor wave of genome activation is first detected in zebrafish. We identified the miR-430 cluster as having excessive copy number and the highest density of Pol-II-transcribed promoters in the genome, and this is required for forming the transcription body. However, this transcription body is not essential for, nor does it encompasse, minor wave transcription globally. Instead, distinct minor-wave-specific promoter architecture suggests that promoter-autonomous mechanisms regulate the minor wave of genome activation. The minor-wave-specific features also suggest distinct transcription initiation mechanisms between the minor and major waves of genome activation.

Original languageEnglish
Pages (from-to)155-170.e8
Number of pages24
JournalDevelopmental Cell
Volume58
Issue number2
DOIs
Publication statusPublished - 23 Jan 2023

Bibliographical note

Funding Information:
This work was funded by a Wellcome Trust Investigator Award ( 106955/Z/15/Z ) and funding from the MDS Research Development Fund to F.M. and was supported in part (S.B.) by the Intramural Research Program of the NHGRI ( ZIAHG200386-06 ). We thank Genomics Birmingham for sequencing, the imaging facility of the Technology Hub core, and the BMSU facility at the University of Birmingham. We thank S. Branford and J.-B. Cazier for support from the University of Birmingham BlueBEAR/CaStLeS high performance computing cluster. We also thank A. Jimenez-Gonzalez for embryo injections and P. Balwierz for advice on gene copy-number calculations. We thank M. Lagha for their smiFISH protocol. We thank Darius Balciunas for providing the pDB783:Xla.crygc-attP-Gal4vp16-14UAS:eGFP plasmid.

Publisher Copyright:
© 2022 The Authors

Keywords

  • core promoter features
  • minor wave
  • miR-430
  • RNA Pol II
  • transcription body
  • zygotic genome activation

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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