The nuclear periphery is a scaffold for tissue-specific enhancers

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(11), P. 6181 - 6195

Published: April 30, 2021

Abstract Nuclear architecture influences gene regulation and cell identity by controlling the three-dimensional organization of genes their distal regulatory sequences, which may be far apart in linear space. The genome is functionally spatially segregated eukaryotic nucleus with transcriptionally active regions nuclear interior separated from repressive regions, including those at periphery. Here, we describe identification a novel type peripheral chromatin domain that enriched for tissue-specific transcriptional enhancers. Like other periphery, these are marked H3K9me2. But unlike Lamina-Associated Domains (LADs), novel, enhancer-rich domains have limited Lamin B interaction. We therefore refer to them as H3K9me2-Only (KODs). In mouse embryonic stem cells, KODs found Hi-C-defined A compartments feature relatively accessible chromatin. characterized low expression enhancers located bear histone marks an inactive or poised state. These results indicate organize subset inactive, hypothesize play role facilitating perhaps constraining enhancer-promoter interactions underlying spatiotemporal programs differentiation development.

Language: Английский

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Diversity of Nuclear Lamin A/C Action as a Key to Tissue-Specific Regulation of Cellular Identity in Health and Disease

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Oct. 13, 2021

A-type lamins are the main structural components of nucleus, which mainly localized at nucleus periphery. First all, lamins, together with B-type and proteins inner nuclear membrane, form a stiff structure-the lamina. Besides maintaining cell shape, play critical role in many cellular events, such as gene transcription epigenetic regulation. Nowadays it is clear that very important determining fate decisions. Various mutations genes encoding lead to damages different types tissues humans, collectively known laminopathies, involved regulation differentiation stemness. However, mechanisms this remain unclear. In review, we discuss how can execute their regulatory status cell. We have summarized recent data focused on lamin A/C action identity development stem cells origin. also knowledge promote further research toward deeper understanding laminopathies.

Language: Английский

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CTCF and cohesin promote focal detachment of DNA from the nuclear lamina

Genome biology, Journal Year: 2022, Volume and Issue: 23(1)

Published: Sept. 1, 2022

Abstract Background Lamina-associated domains (LADs) are large genomic regions that positioned at the nuclear lamina. It has remained largely unclear what drives positioning and demarcation of LADs. Because insulator protein CTCF is enriched LAD borders, it was postulated binding could position some boundaries, possibly through its function in stalling cohesin hence preventing invading into LAD. To test this, we mapped genome–nuclear lamina interactions mouse embryonic stem cells after rapid depletion other perturbations dynamics. Results contribute to a sharp transition while LADs maintained these proteins, also borders marked by CTCF. may thus reinforce but do not these. sites within locally detached from for accessible DNA active histone modifications. Remarkably, despite being strongly correlated with genome inactivity, this remains local detachment lost following depletion. At chromosomal scale, stabilization unloading factor WAPL quantitatively affect interactions, indicative perturbed nucleus. Finally, H3K27me3 CTCF-marked find no evidence an interplay between on interactions. Conclusions These findings illustrate primary determinants patterns. Rather, proteins modulate NL

Language: Английский

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TET2 modulates spatial relocalization of heterochromatin in aged hematopoietic stem and progenitor cells

Nature Aging, Journal Year: 2023, Volume and Issue: 3(11), P. 1387 - 1400

Published: Oct. 26, 2023

Language: Английский

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Choreography of lamina‐associated domains: structure meets dynamics

FEBS Letters, Journal Year: 2023, Volume and Issue: 597(22), P. 2806 - 2822

Published: Nov. 1, 2023

Lamina‐associated domains are large regions of heterochromatin positioned at the nuclear periphery. These have been implicated in gene repression, especially context development. In mammals, LAD organization is dependent on lamins, inner membrane proteins, and chromatin state. addition, readers modifier proteins this organization, potentially serving as molecular tethers that interact with both envelope chromatin. More recent studies focused teasing apart rules govern dynamic how turn, relates to regulation overall 3D genome organization. This review highlights mammalian cells uncovering factors instruct choreography re‐organization, dynamics lamina, including interphase through mitotic exit, when re‐established, well intra‐LAD subdomain variations.

Language: Английский

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