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Identification of Chromatin proteins involved in gene repression in lamina-associated domains

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261955 | GEO | 2024/07/10

REPOSITORIES: GEO

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Chromatin protein complexes involved in gene repression in lamina-associated domains

Project description:Lamina-associated domains (LADs) are large chromatin regions that are associated with the nuclear lamina (NL) and form a repressive environment for transcription. The molecular players that mediate gene repression in LADs are currently unknown. Here, we performed FACS-based whole-genome genetic screens in human cells using LAD-integrated fluorescent reporters to identify such regulators. Surprisingly, the screen identified very few NL proteins, but revealed roles for dozens of known chromatin regulators. Among these are the negative elongation factor (NELF) complex and interacting factors involved in RNA polymerase pausing, suggesting that regulation of transcription elongation is a mechanism to repress transcription in LADs. Furthermore, the chromatin remodeler complex BAF and the activation complex Mediator can work both as activators and repressors in LADs, depending on the local context and possibly by rewiring heterochromatin. Our data indicate that the fundamental regulators of transcription and chromatin remodeling, rather than interaction with NL proteins, play a major role in transcription regulation within LADs.

| S-SCDT-10_1038-S44318-024-00214-1 | biostudies-other

Identification of Chromatin proteins involved in gene repression in lamina-associated domains (RNA-Seq)

Project description:Lamina-associated domains (LADs) are large chromatin regions that are associated with the nuclear lamina and form a repressive environment for transcription. The molecular players that mediate gene repression in LADs are currently unknown. Here we performed a full-genome genetic screen in human cells using LAD-integrated fluorescent reporters to identify such regulators. Surprisingly, the screen identified very few lamina proteins, but revealed roles for dozens of known chromatin regulators. Among these are the negative elongation factor (NELF) complex and interacting factors, suggesting that regulation of RNA polymerase pausing can be a mechanism to repress transcription in LADs. Furthermore, the chromatin remodeler complex BAF and the activation complex Mediator can work both as activators and repressors in LADs, depending on the local context and possibly rewiring of heterochromatin. Our data suggest that fundamental regulatory steps of the transcription process and chromatin remodeling, rather than interaction with NL proteins, have a major role in the regulation of transcription in LADs.

2024-07-10 | GSE261953 | GEO

Identification of Chromatin proteins involved in gene repression in lamina-associated domains (pA-DamID)

2024-07-10 | GSE261868 | GEO

Identification of Chromatin proteins involved in gene repression in lamina-associated domains

Project description:Identification of Chromatin proteins involved in gene repression in lamina-associated domains

| PRJNA1089617 | ENA

Identification of Chromatin proteins involved in gene repression in lamina-associated domains (pA-DamID)

Project description:Identification of Chromatin proteins involved in gene repression in lamina-associated domains (pA-DamID)

| PRJNA1089230 | ENA

Identification of Chromatin proteins involved in gene repression in lamina-associated domains (RNA-Seq)

Project description:Identification of Chromatin proteins involved in gene repression in lamina-associated domains (RNA-Seq)

| PRJNA1089636 | ENA

Lamina Associated Domains dependent of chromatin state and A-type lamins

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-03-27 | GSE97095 | GEO

Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford Progeria Syndrome

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-08 | GSE150138 | GEO

A molecular mechanism for compartmentalization and silencing of chromatin domains at the nuclear lamina

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-02-24 | GSE36049 | GEO

Gene Regulatory Interactions at Lamina-Associated Domains.

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

| S-EPMC9957430 | biostudies-literature

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