A dynamic role for transcription factors in restoring transcription through mitosis

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(2), P. 821 - 830

Published: March 25, 2024

Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian suggested transcription factors (TFs) mark genes swift reactivation, a phenomenon termed ‘mitotic bookmarking’, but conflicting data emerged regarding TF presence on mitotic chromosomes. Recent advancements live-cell imaging fixation-free genomics challenge conventional belief universal formaldehyde fixation, revealing dynamic interactions during mitosis. Here, we review recent provide examples of at least four modes TF–DNA interaction mitosis molecular mechanisms govern these interactions. Additionally, explore impact initiation post-mitosis. Taken together, call paradigm shift toward model behavior mitosis, underscoring need incorporating dynamics mechanistic models re-establishing

Language: Английский

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Nr5a2 is dispensable for zygotic genome activation but essential for morula development

Science, Journal Year: 2024, Volume and Issue: 386(6717)

Published: Oct. 3, 2024

Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify lineages constituting blastocyst. Although TFs specifying blastocyst's are well characterized, those playing earlier roles remain poorly defined. Using mouse models of TF

Language: Английский

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Emerging Roles for Transcription Factors During Mitosis

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 263 - 263

Published: Feb. 12, 2025

The genome is dynamically reorganized, partitioned, and divided during mitosis. Despite their role in organizing interphase chromatin, transcription factors were largely believed to be mitotic spectators evicted from chromatin mitosis, only able reestablish position on DNA upon entry into G1. However, a panoply of evidence now contradicts this early belief. Numerous are known remain active mitosis achieve diverse purposes, including chromosome condensation, regulation the centromere/kinetochore function, control centrosome homeostasis. Inactivation results segregation errors, key features cancer. Moreover, production centromere-derived transcripts also play roles maintaining chromosomal stability. Finally, many associated with instability through poorly defined mechanisms. Herein, we will review emerging focus promoting faithful sister chromatids.

Language: Английский

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Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Abstract Prior studies showed that structural loops collapse upon acute cohesin depletion, while regulatory enhancer-promoter (E-P) largely persist, consistent with minimal transcriptional changes. However, these studies, conducted in asynchronous cells, could not resolve whether is required for the establishment of interactions and activation during cell division or state transitions. To address this gap, we degraded RAD21, a core subunit, naïve mouse embryonic stem cells (ESCs) transitioning from mitosis to G1 either self-renewal condition differentiation toward formative pluripotency. Although most failed be re-established without cohesin, about 35% reformed at normal higher frequencies. Cohesin-independent characteristics strong active enhancers promoters significant association H3K27ac mitotic bookmarks. inhibition CBP/p300 exit did impact cohesin-independent interactions, suggesting presence complex compensatory mechanisms. At level, depletion induced only minor changes, supporting post-mitotic reactivation independent cohesin. The few genes impaired were directly bound by RAD21 their promoters, engaged many loops, located within strongly insulated TADs low gene density. Importantly, degrading M-to-G1 transition EpiLC signals revealed larger group susceptible genes, including key signature transcription factors. Impaired was partly due failure establish de novo EpiLC-specific absence These experiments locus-specific context-specific dependencies between E-P transcription.

Language: Английский

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Molecular mechanisms altering cell identity in cancer

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

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3D genome folding in epigenetic regulation and cellular memory

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The 3D folding of the genome is tightly linked to its epigenetic state which maintains gene expression programmes. Although relationship between and organisation highly context dependent, emerging as a novel layer reinforce stabilise transcriptional states. Whether regulatory information carried in could be transmitted through mitosis an area active investigation. In this review, we discuss nuclear organisation, well interplay regulation folding. We also consider architectural remodelling nuclei cells enter exit mitosis, evaluate potential contribute cellular memory.

Language: Английский

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Dynamics of microcompartment formation at the mitosis-to-G1 transition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

As cells exit mitosis and enter G1, mitotic chromosomes decompact transcription is reestablished. Previously, Hi-C studies showed that essentially all interphase 3D genome features including A/B-compartments, TADs, CTCF loops, are lost during mitosis. However, remains insensitive to such as microcompartments, nested focal interactions between cis -regulatory elements (CREs). We therefore applied Region Capture Micro-C from G1. Unexpectedly, we observe microcompartments in prometaphase, which further strengthen ana/telophase before gradually weakening Loss of loop extrusion through condensin depletion differentially impacts large suggesting they partially distinct. Using polymer modeling, show microcompartment formation favored by chromatin compaction disfavored activity, explaining why likely provides a particularly favorable environment. Our results suggest CREs exhibit intrinsic homotypic affinity leading formation, may explain transient transcriptional spiking observed upon exit.

Language: Английский

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Exploring the reciprocity between pioneer factors and development

Development, Journal Year: 2024, Volume and Issue: 151(13)

Published: July 1, 2024

ABSTRACT Development is regulated by coordinated changes in gene expression. Control of these expression largely governed the binding transcription factors to specific regulatory elements. However, packaging DNA into chromatin prevents many factors. Pioneer overcome this barrier owing unique properties that enable them bind closed chromatin, promote accessibility and, so doing, mediate additional activate Because properties, pioneer act at top gene-regulatory networks and drive developmental transitions. Despite ability target motifs have cell type-specific occupancy activity. Thus, context clearly shapes pioneer-factor function. Here, we discuss reciprocal interplay between development: how control fate cellular environment influences

Language: Английский

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Targeting estrogen-related receptors to mitigate tumor resistance: A comprehensive approach to bridging cellular energy metabolism

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1880(1), P. 189256 - 189256

Published: Dec. 31, 2024

Language: Английский

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Bookmarking pluripotency genes

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(3), P. 160 - 160

Published: Feb. 2, 2024

Language: Английский

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