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

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

doi:10.1016/j.devcel.2022.12.007

Cited by 29 publications

(29 citation statements)

References 105 publications

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“…3O). This locus has been estimated to have >300 promoters capable of transcribing primary miR-430 transcripts (42), which is consistent with the ~1800 mature miR-430 genes detected in our assembly (fig. S7, C and D).…”

Section: Rna Pol II Forms String Nanostructures Associated With Nasce...supporting

confidence: 87%

Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin

Pownall

Miao

Vejnar

et al. 2023

Science

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Nanoscale chromatin organization regulates gene expression. Although chromatin is notably reprogrammed during zygotic genome activation (ZGA), the organization of chromatin regulatory factors during this universal process remains unclear. In this work, we developed chromatin expansion microscopy (ChromExM) to visualize chromatin, transcription, and transcription factors in vivo. ChromExM of embryos during ZGA revealed how the pioneer factor Nanog interacts with nucleosomes and RNA polymerase II (Pol II), providing direct visualization of transcriptional elongation as string-like nanostructures. Blocking elongation led to more Pol II particles clustered around Nanog, with Pol II stalled at promoters and Nanog-bound enhancers. This led to a new model termed "kiss and kick", in which enhancer–promoter contacts are transient and released by transcriptional elongation. Our results demonstrate that ChromExM is broadly applicable to study nanoscale nuclear organization.

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Section: Rna Pol II Forms String Nanostructures Associated With Nasce...supporting

confidence: 87%

Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin

Pownall

Miao

Vejnar

et al. 2023

Science

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“…After dye incubation, embryos were washed and kept in a Triptolide solution for further development and imaging. Triptolide concentration and handling are comparable to previous reports 104,105 .…”

Section: Methodssupporting

confidence: 87%

Increasingly efficient chromatin binding of cohesin and CTCF supports chromatin architecture formation during zebrafish embryogenesis

Coßmann,

Kos,

Varamogianni-Mamatsi

et al. 2023

Preprint

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The three-dimensional folding of chromosomes is essential for nuclear functions such as DNA replication and gene regulation. The emergence of chromatin architecture is thus an important process during embryogenesis. To shed light on the molecular and kinetic underpinnings of chromatin architecture formation, we characterized biophysical properties of cohesin and CTCF binding to chromatin and their changes upon cofactor depletion using single-molecule imaging in live developing zebrafish embryos. We found that chromatin-bound fractions of both cohesin and CTCF increased significantly between the 1000-cell and shield stages, which we could explain through changes in both their association and dissociation rates. Moreover, increasing binding of cohesin restricted chromatin motion, potentially via loop extrusion, and showed distinct stage-dependent nuclear distribution. Polymer simulations with experimentally derived parameters recapitulated the experimentally observed gradual emergence of chromatin architecture. Our findings suggest a kinetic framework of chromatin architecture formation during zebrafish embryogenesis.

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“…Notably, it detects the promoters of the first wave of zygotic genome activation (ZGA), primarily coming from a dedicated gene cluster on chromosome 4 (clusters C3,9-10Y) (Figure 10A). Cluster C9Y belongs to genes encoding mir-430, which are present in hundreds of moderately divergent copies (Hadzhiev et al 2023), and whose miRNA product specifically targets maternal RNAs for degradation (Giraldez et al 2006; Bazzini, Lee, and Giraldez 2012). The ability to detect these architectures in a sample dominated by maternal RNA shows that seqArchR is a powerful tool for characterising regulatory transitions at the promoter level.…”

Section: Resultsmentioning

confidence: 99%

Identifying promoter sequence architectures via a chunking-based algorithm using non-negative matrix factorisation

Nikumbh

Lenhard

2023

Preprint

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Core promoters are stretches of DNA at the beginning of genes that contain information that facilitates the binding of transcription initiation complex. Different functional subsets of genes have core promoters with distinct architectures and characteristic motifs. Some of these motifs inform the selection of transcription start sites (TSS). By discovering motifs with fixed distances from known TSS positions, we could in principle classify promoters into different functional groups.Due to the variability and overlap of architectures, promoter classification is a difficult task that requires new approaches. In this study, we present a new method based on non-negative matrix factorisation (NMF) and the associated software called seqArchR that clusters promoter sequences based on their motifs at near-fixed distances from a reference point, such as TSS. When combined with experimental data from CAGE, seqArchR can efficiently identify TSS-directing motifs, including known ones like TATA, DPE, and nucleosome positioning signal, as well as novel lineage-specific motifs and the function of genes associated with them. By using seqArchR on developmental time courses, we reveal how relative use of promoter architectures changes over time with stage-specific expression.seqArchR is a powerful tool for initial genome-wide classification and functional characterization of promoters. Its use cases are more general: it can also be used to discover any motifs at near-fixed distances from a reference point, even if they are present in only a small subset of sequences. seqArchR is available athttp://www.bioconductor.org/packages/seqArchR.

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

Cited by 29 publications

References 105 publications

Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin

Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin

Increasingly efficient chromatin binding of cohesin and CTCF supports chromatin architecture formation during zebrafish embryogenesis

Identifying promoter sequence architectures via a chunking-based algorithm using non-negative matrix factorisation

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