Jul 5, 2016

Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments

BioRxiv : the Preprint Server for Biology
Michael I RobsonEric C Schirmer

Abstract

The 3D organization of the genome changes concomitantly with expression changes during hematopoiesis and immune activation. However, studies of this phenomenon have focused either on lamina-associated domains (LADs) or on topologically-associated domains (TADs), defined by preferential local chromatin interactions, and chromosome compartments, defined as higher-order interactions between TADs in functionally similar states. However, few studies have investigated how these affect one another. To address this, we mapped LADs using Lamin B1-DamID during Jurkat T-cell activation, finding significant genome re-organization at the nuclear periphery dominated by release of loci frequently important for T-cell function. To assess how these changes at the nuclear periphery influence wider genome organization, our DamID datasets were contrasted with TAD contact domains and compartments identified with high resolution in the GM12878 lymphoblastoid cell line. Features of specific repositioning events were then tested by fluorescence in situ hybridization. First, considerable overlap between TAD contact domains and LADs was observed and we found that the TAD repositioned as a unit during T-cell activation. Second, sub-compartments of the A ...Continue Reading

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Mentioned in this Paper

Study
Fluorescent in Situ Hybridization
Inferior
Body Fluid Compartments
Genome
Genes
Three-dimensional
DNA Topology Regulation
Blade - plant part
IgA1

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