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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

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

Identification of proteins involved in the pathogenesis of colorectal tumor progression

Project description:Primary outcome(s): Measure auto-lysosome function in the cytoplasm by electron microscopy to examine the changes in the number of autophagy.

| 2626385 | ecrin-mdr-crc

Mapping the micro-proteome of the nuclear lamina and lamina-associated domains.

Project description:The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins and large domains of DNA, the so-called lamina-associated domains (LADs), to the periphery of the nucleus. LADs are a large fraction of the mammalian genome that are repressed, in part, by their association to the nuclear periphery. The genesis and maintenance of LADs is poorly understood as are the proteins that participate in these functions. In an effort to identify proteins that reside at the nuclear periphery and potentially interact with LADs, we have taken a two-pronged approach. First, we have undertaken an interactome analysis of the inner nuclear membrane bound LAP2β to further characterize the nuclear lamina proteome. To accomplish this, we have leveraged the BioID system, which previously has been successfully used to characterize the nuclear lamina proteome. Second, we have established a system to identify proteins that bind to LADs by developing a chromatin-directed BioID system. We combined the BioID system with the m6A-tracer system which binds to LADs in live cells to identify both LAD proximal and nuclear lamina proteins. In combining these datasets, we have further characterized the protein network at the nuclear lamina, identified putative LAD proximal proteins and found several proteins that appear to interface with both micro-proteomes. Importantly, several proteins essential for LAD function, including heterochromatin regulating proteins related to H3K9 methylation, were identified in this study.

| S-EPMC8008952 | biostudies-literature

Systematic identification of RNA-binding proteins and tethered domains that activate exon splicing inclusion

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

2023-09-22 | GSE232599 | GEO

Lamina-associated domains: peripheral matters and internal affairs.

Project description:At the nuclear periphery, associations of chromatin with the nuclear lamina through lamina-associated domains (LADs) aid functional organization of the genome. We review the organization of LADs and provide evidence of LAD heterogeneity from cell ensemble and single-cell data. LADs are typically repressive environments in the genome; nonetheless, we discuss findings of lamin interactions with regulatory elements of active genes, and the role lamins may play in genome regulation. We address the relationship between LADs and other genome organizers, and the involvement of LADs in laminopathies. The current data lay the basis for future studies on the significance of lamin-chromatin interactions in health and disease.

| S-EPMC7114793 | biostudies-literature

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