Gene Regulatory Interactions at Lamina-Associated Domains DOI Open Access
Julia Madsen‐Østerbye, Mohamed Abdelhalim, Sarah Hazell Pickering

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 334 - 334

Published: Jan. 28, 2023

The nuclear lamina provides a repressive chromatin environment at the periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside local euchromatic contexts and expressed. How these regulated whether they able to interact with regulatory elements remain unclear. Here, we integrate publicly available enhancer-capture Hi-C data our own state transcriptomic datasets show that inferred enhancers of active LADs form connections other within outside LADs. Fluorescence situ hybridization analyses proximity changes between differentially expressed distant upon induction adipogenic differentiation. We also provide evidence involvement lamin A/C, but not B1, repressing border an in-LAD region topological domain. Our favor model where spatial topology is compatible gene expression this dynamic compartment.

Language: Английский

Biophysical forces mediated by respiration maintain lung alveolar epithelial cell fate DOI Creative Commons
Kazushige Shiraishi, Parisha P. Shah, Michael P. Morley

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1478 - 1492.e15

Published: March 1, 2023

Language: Английский

Citations

71
An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype DOI Creative Commons
Parisha P. Shah, Kathleen C. Keough, Ketrin Gjoni

et al.

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: Jan. 23, 2023

Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via silencing. Unlike many histone modifications chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human types, which limits our understanding role peripheral plays development disease.

Language: Английский

Citations

43
Epigenetic regulatory layers in the 3D nucleus DOI Creative Commons
Andréa Willemin, Dominik Szabó, Ana Pombo

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(3), P. 415 - 428

Published: Jan. 18, 2024

Nearly 7 decades have elapsed since Francis Crick introduced the central dogma of molecular biology, as part his ideas on protein synthesis, setting fundamental rules sequence information transfer from DNA to RNAs and proteins. We learned that gene expression is finely tuned in time space, due activities proteins regulatory elements, through cell-type-specific three-dimensional conformations genome. Here, we review major advances genome biology discuss a set regulation highlight how various biomolecular assemblies lead formation structural features within nucleus, with roles transcriptional control. conclude by suggesting further developments will help capture complex, dynamic, often spatially restricted events govern mammalian cells.

Language: Английский

Citations

19
Pioneer factors — key regulators of chromatin and gene expression DOI
Martha L. Bulyk, Jacques Drouin, Melissa M. Harrison

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(12), P. 809 - 815

Published: Sept. 22, 2023

Language: Английский

Citations

27
Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism DOI Creative Commons
Emily M. Pujadas-Liwag,

Xiaolong Wei,

Nicolas Acosta

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 22, 2024

B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous using Auxin-inducible degron technology.

Language: Английский

Citations

14
Pioneer factor Pax7 initiates two-step cell-cycle-dependent chromatin opening DOI
Arthur Gouhier,

Justine Dumoulin-Gagnon,

Vincent Lapointe-Roberge

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(1), P. 92 - 101

Published: Jan. 1, 2024

Language: Английский

Citations

13
Nuclear envelope and chromatin choreography direct cellular differentiation DOI Creative Commons
Arshad Arjunan Nair,

Jayati Khanna,

Jashan Kler

et al.

Nucleus, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 12, 2025

The nuclear envelope plays an indispensable role in the spatiotemporal organization of chromatin and transcriptional regulation during intricate process cell differentiation. This review outlines distinct regulatory networks between proteins, transcription factors epigenetic modifications controlling expression lineage-specific genes Nuclear lamina with its associated proteins organize heterochromatin via Lamina-Associated Domains (LADs), proximal to periphery. Since is mechanosensitive, we critically examine impact extracellular forces on differentiation outcomes. spanned by pore complexes which, addition their central transport, are organization. Furthermore, mutations disrupt differentiation, resulting developmental disorders. Investigating underlying controlled mechanisms remodelling lineage commitment will accelerate our fundamental understanding biology regenerative medicine.

Language: Английский

Citations

1
Mechanobiology of the nucleus during the G2-M transition DOI Creative Commons
Joana T. Lima, Jorge G. Ferreira

Nucleus, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 27, 2024

Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, nucleus has emerged as a regulator of cellular response to stimuli. Cell cycle progression regulated cyclin-CDK complexes. Recent studies demonstrated these are signals, highlighting interdependence mechanics cell regulation. In particular, transition from G2 mitosis (G2-M) shows significant changes in nuclear structure organization, ranging pore complex (NPC) lamina disassembly chromosome condensation. The remodeling mechanically active components indicates mitotic entry particularly sensitive Here, we address how crosstalk with determine timing efficiency G2-M transition. Finally, discuss deregulation consequences for mitosis.

Language: Английский

Citations

6
Choreography of lamina‐associated domains: structure meets dynamics DOI Open Access

Nicholas S. Alagna,

Tiera I. Thomas,

Katherine L. Wilson

et al.

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

Citations

15
Expansion in situ genome sequencing links nuclear abnormalities to hotspots of aberrant euchromatin repression DOI
Ajay Labade, Zachary Chiang,

Caroline Comenho

et al.

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

Published: Sept. 26, 2024

Microscopy and genomics are both used to characterize cell function, but approaches connect the two types of information lacking, particularly at subnuclear resolution. While emerging multiplexed imaging methods can simultaneously localize genomic regions nuclear proteins, their ability accurately measure DNA-protein interactions is constrained by diffraction limit optical microscopy. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables DNA superresolution localization proteins single cells. We applied ExIGS fibroblast cells derived from an individual with Hutchinson-Gilford progeria syndrome how variation morphology affects spatial chromatin organization. Using this data, discovered lamin abnormalities linked hotspots aberrant euchromatin repression may erode identity. Further, show heterogeneously increase repressive environment nucleus tissues aged These results demonstrate serve as generalizable platform for connecting changes gene regulation across disease contexts.

Language: Английский

Citations

5