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A lamina-associated domain border governs nuclear lamina interactions, transcription and recombination of the Tcrb locus.

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

ORGANISM(S): Mus musculus

PROVIDER: GSE116954 | GEO | 2018/10/22

REPOSITORIES: GEO

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A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus.

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A lamina-associated domain border governs nuclear lamina interactions, transcription and recombination of the Tcrb locus [DamID]

Project description:Tcrb locus V(D)J recombination is regulated by positioning at the nuclear periphery. Here we used DamID to profile Tcrb locus interactions with the nuclear lamina at high-resolution. We identified a lamina-associated domain (LAD) border composed of several CTCF binding elements that segregates active non-LAD from inactive LAD regions of the locus. Deletion of the LAD border caused an enhancer-dependent spread of H3K27ac from the active recombination center into recombination center-proximal LAD chromatin. This was associated with a disruption to LAD organization, increased chromatin looping to the recombination center, and increased transcription and recombination of recombination center-proximal gene segments. Our results show that a Tcrb locus LAD and LAD border are critical components of Tcrb locus gene regulation and suggest that LAD borders may generally function to constrain the activity of nearby enhancers.

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A lamina-associated domain border governs nuclear lamina interactions, transcription and recombination of the Tcrb locus [ChIP-seq]

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A lamina-associated domain border governs nuclear lamina interactions, transcription and recombination of the Tcrb locus.

Project description:A lamina-associated domain border governs nuclear lamina interactions, transcription and recombination of the Tcrb locus.

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Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

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Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions

Project description:Proper genome functionality is underpinned by the non-random, spatial or ganisation of chromatin. At the periphery of the nucleus, the association of chr omatin with the nuclear lamina is thought to facilitate both structural organisa tion and regulation of gene expression. Except for a small number of individual loci, the regions of the human genome that locate at the nuclear lamina have not been identified. Here we used DamID to map the interaction sites of lamin B1 at high resolution in human fibroblasts. We show that almost half of the human gen ome preferentially associates with the nuclear lamina. Chromatin-lamina interact ions occur via sharply demarcated domains of up to several megabases in size, wh ich are bordered by similar sized domains that do not associate with the lamina. Lamina associated domains (LADs) are typified by low gene density and low gene expression levels. This is reflected by low levels of PolII binding and histone modification H3K4me2, in combination with enrichment of H3K27me3 (and H3K9?). A considerable subset of LADs is flanked by active promoters pointing outwards, or by the insulator protein CTCF, suggesting possible mechanisms of LAD confinemen t. Finally, we found that chromosome re-arrangements occur more frequently betwe en loci located either within or outside LADs. The identification of enormous, s harply defined stretches of the human genome that associate with the nuclear lam ina provides unprecedented insights into the 3D organisation of chromatin within the nucleus. Our results reveal the division of the human genome into periphera l and internal domains, which is echoed in genome functionality. Keywords: DamID

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Local rewiring of genome-nuclear lamina interactions by transcription.

Project description: Not available

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