RNA polymerase II is required for spatial chromatin reorganization following exit from mitosis

Zhang, Shu; Übelmesser, Nadine; Josipović, Nataša; Forte, Giada; Slotman, Johan A.; Chiang, Michael; Gothe, Henrike Johanna; Gusmao, Eduardo Gade; Becker, Christian; Altmüller, Janine; Houtsmuller, Adriaan B.; Roukos, Vassilis; Wendt, Kerstin S.; Marenduzzo, Davide; Papantonis, Argyris

doi:10.1126/sciadv.abg8205

Cited by 84 publications

(60 citation statements)

References 82 publications

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“…Acute ablation of any of the three RNA polymerases with an auxin-inducible degron had negligible effects on any feature of genome architecture, including TADs (Jiang et al, 2020). The resolution of this study may not have been high enough to discern subtle effects, and a similar experimental approach showed that whereas interphase chromatin was indeed largely unaltered, resetting of TADs just after mitosis was affected by loss of RNA polymerase II (Zhang et al, 2021). As an alternative means of testing the direct effect of transcription on chromatin topology, another study used CRISPR-activation (CRISPRa; Gilbert et al, 2013) to ectopically induce two specific genes in ESCs: Sox4 and Zfp608 (Bonev et al, 2017).…”

Section: Introductionmentioning

confidence: 98%

Context-dependent transcriptional remodeling of TADs during differentiation

Chahar

Zouari

Salari

et al. 2022

Preprint

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Metazoan chromosomes are organized into discrete domains (TADs), believed to contribute to the regulation of transcriptional programs. Despite extensive correlation between TAD organization and gene activity, a direct mechanistic link is unclear, with perturbation studies often showing little effect. To follow TAD dynamics during development, we used Capture Hi-C to interrogate the TADs around key differentially expressed genes during mouse thymocyte maturation, uncovering specific remodeling events. Notably, one TAD boundary was broadened to accommodate RNA polymerase elongation past the border, and sub-domains were formed around some activated genes without changes in CTCF binding. The ectopic induction of one gene was sufficient to recapitulate microdomain formation in embryonic stem cells, providing strong evidence that transcription can directly remodel chromatin structure. These results suggest that transcriptional processes drive complex, but non-universal, chromosome folding patterns that can be important in certain genomic contexts.

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Section: Introductionmentioning

confidence: 98%

Context-dependent transcriptional remodeling of TADs during differentiation

Chahar

Zouari

Salari

et al. 2022

Preprint

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“…Two recent studies shine new light on how transcription modulates proper domain formation in the chromatin. In the first study, Pol II was acutely depleted in human DLD-1 cell line to assess its contribution to genome folding [ 122 ]. Hi-C analysis of chromatin folding on G1-sorted cells after extended depletion (14 hours) revealed only a mild disruption of TADs.…”

Section: Transcription On a Megabase Scalementioning

confidence: 99%

Mechanical determinants of chromatin topology and gene expression

Jha

Levens

Kouzine

2022

Nucleus

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The compaction of linear DNA into micrometer-sized nuclear boundaries involves the establishment of specific three-dimensional (3D) DNA structures complexed with histone proteins that form chromatin. The resulting structures modulate essential nuclear processes such as transcription, replication, and repair to facilitate or impede their multi-step progression and these contribute to dynamic modification of the 3D-genome organization. It is generally accepted that protein–protein and protein–DNA interactions form the basis of 3D-genome organization. However, the constant generation of mechanical forces, torques, and other stresses produced by various proteins translocating along DNA could be playing a larger role in genome organization than currently appreciated. Clearly, a thorough understanding of the mechanical determinants imposed by DNA transactions on the 3D organization of the genome is required. We provide here an overview of our current knowledge and highlight the importance of DNA and chromatin mechanics in gene expression.

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“…Importantly, reducing H3K27ac with a new selective inhibitor of the catalytic subunit of CBP/p300 impairs gene reactivation during mitotic exit (even if inhibition only takes place in anaphase/telophase), indicating H3K27ac recovery during this time period is important for reactivation [ 11 , 12 ]. Interestingly, depleting mitotic RNA pol II leads to reduced H3K27ac levels and cohesin loading in early G1, hinting at a possible link between canonical TF activity and H3K27ac deposition during M-G1 [ 72 ]. Altogether, these observations also cement the importance M-G1 time-window may have for cell identity maintenance and cell fate changes.…”

Section: Tf Activity and Waves Of Transcriptional Reactivation During...mentioning

confidence: 99%

Function and regulation of transcription factors during mitosis-to-G1 transition

2022

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During cell division, drastic cellular changes characteristic of mitosis result in the inactivation of the transcriptional machinery, and global downregulation of transcription. Sequence-specific transcription factors (TFs) have thus been considered mere bystanders, devoid of any regulatory function during mitosis. This view changed significantly in recent years, upon the conclusion that many TFs associate with condensed chromosomes during cell division, even occupying a fraction of their genomic target sites in mitotic chromatin. This finding was at the origin of the concept of mitotic bookmarking by TFs, proposed as a mechanism to propagate gene regulatory information across cell divisions, by facilitating the reactivation of specific bookmarked genes. While the underlying mechanisms and biological significance of this model remain elusive, recent developments in this fast-moving field have cast new light into TF activity during mitosis, beyond a bookmarking role. Here, we start by reviewing the most recent findings on the complex nature of TF–chromatin interactions during mitosis, and on mechanisms that may regulate them. Next, and in light of recent reports describing how transcription is reinitiated in temporally distinct waves during mitosis-to-G1 transition, we explore how TFs may contribute to defining this hierarchical gene expression process. Finally, we discuss how TF activity during mitotic exit may impact the acquisition of cell identity upon cell division, and propose a model that integrates dynamic changes in TF–chromatin interactions during this cell-cycle period, with the execution of cell-fate decisions.

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RNA polymerase II is required for spatial chromatin reorganization following exit from mitosis

Abstract: Following exit from mitosis, RNA Pol II is required for reestablishing 3D genome folding by loading cohesin complexes onto DNA.

Cited by 84 publications

References 82 publications

Context-dependent transcriptional remodeling of TADs during differentiation

Context-dependent transcriptional remodeling of TADs during differentiation

Mechanical determinants of chromatin topology and gene expression

Function and regulation of transcription factors during mitosis-to-G1 transition

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