Chromatin condensation via the condensin II complex is required for peripheral T-cell quiescence

Rawlings, Jason S.; Gatzka, Martina; Thomas, Paul G.

doi:10.1038/emboj.2010.314

Cited by 131 publications

(152 citation statements)

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“…The extensive electron-dense peripheral heterochromatin of resting T cells dissipates during activation concomitantly with the induction of immunogenic genes (Hirschhorn et al 1971;Pompidou et al 1984;Manteifel et al 1992;Rawlings et al 2011). However, it is unclear whether this reorganization is wholescale or whether there is also more specific reorganization for immune activation.…”

Section: Mapping Gene Expression and Repositioning Changes During T-cmentioning

confidence: 99%

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

et al. 2017

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The 3D organization of the genome changes concomitantly with expression changes during hematopoiesis and immune activation. Studies 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 sharing 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 reorganization 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 data sets were contrasted with TADs and compartments. Features of specific repositioning events were then tested by fluorescence in situ hybridization during T-cell activation. First, considerable overlap between TADs and LADs was observed with the TAD repositioning as a unit. Second, A1 and A2 subcompartments are segregated in 3D space through differences in proximity to LADs along chromosomes. Third, genes and a putative enhancer in LADs that were released from the periphery during T-cell activation became preferentially associated with A2 subcompartments and were constrained to the relative proximity of the lamina. Thus, lamina associations influence internal nuclear organization, and changes in LADs during T-cell activation may provide an important additional mode of gene regulation.

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Section: Mapping Gene Expression and Repositioning Changes During T-cmentioning

confidence: 99%

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

et al. 2017

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“…Thus, this particular mutation causes a specific defect in T-cell development and a failure in normal immune response (Gosling et al 2008) while preserving the essential function of condensin II. A more recent study has reported that nuclear chromatin rapidly condenses during thymocyte development in a condensin II-dependent manner and that this condensation is required for proper T-cell development and maintenance of the quiescent state (Rawlings et al 2011). Upon T-cell activation, the chromatin decondenses again, making the transcriptional activator Stat5 accessible to its target promoters.…”

Section: T-cell Developmentmentioning

confidence: 99%

Condensins: universal organizers of chromosomes with diverse functions

2012

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Condensins are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. Most eukaryotic species have two different types of condensin complexes, known as condensins I and II, that fulfill nonoverlapping functions and are subjected to differential regulation during mitosis and meiosis. Recent studies revealed that the two complexes contribute to a wide variety of interphase chromosome functions, such as gene regulation, recombination, and repair. Also emerging are their cell type- and tissue-specific functions and relevance to human disease. Biochemical and structural analyses of eukaryotic and bacterial condensins steadily uncover the mechanisms of action of this class of highly sophisticated molecular machines. Future studies on condensins will not only enhance our understanding of chromosome architecture and dynamics, but also help address a previously underappreciated yet profound set of questions in chromosome biology.

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“…This developmentally regulated process culminates in formation of compact blocks of heterochromatin inside the nuclei and spatial segregation of heterochromatin and euchromatin domains (3). Chromatin condensation prevents certain transcription factors from activating genes in the compact chromatin (4). Recent studies suggest that each tissue type has its own unique program that orchestrates tissue maturation, with specific sets of chromatin architectural and remodeling proteins, histone modifications, and micro-RNA (5)(6)(7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Developmentally Regulated Linker Histone H1c Promotes Heterochromatin Condensation and Mediates Structural Integrity of Rod Photoreceptors in Mouse Retina

Popova

Grigoryev

Fan

et al. 2013

Journal of Biological Chemistry

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Background: Heterochromatin condenses in the middle of rod cell nuclei during retina maturation. Results: The level of linker histone H1c increases during retina maturation. Rod photoreceptors in triple H1 knock-out mice have less compact chromatin. Conclusion: H1c is a key architectural factor for chromatin condensation in the rod photoreceptor. Significance: Histone H1c expression may be genetically modified to promote rod photoreceptor maturation and retina integrity.Mature rod photoreceptor cells contain very small nuclei with tightly condensed heterochromatin. We observed that during mouse rod maturation, the nucleosomal repeat length increases from 190 bp at postnatal day 1 to 206 bp in the adult retina. At the same time, the total level of linker histone H1 increased reaching the ratio of 1.3 molecules of total H1 per nucleosome, mostly via a dramatic increase in H1c. Genetic elimination of the histone H1c gene is functionally compensated by other histone variants. However, retinas in H1c/H1e/H1 0 triple knock-outs have photoreceptors with bigger nuclei, decreased heterochromatin area, and notable morphological changes suggesting that the process of chromatin condensation and rod cell structural integrity are partly impaired. In triple knock-outs, nuclear chromatin exposed several epigenetic histone modification marks masked in the wild type chromatin. Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus. During retina development, the H1c gene and its promoter acquired epigenetic patterns typical of rod-specific genes. Our data suggest that histone H1c gene expression is developmentally up-regulated to promote facultative heterochromatin in mature rod photoreceptors.During mammalian development, cells committed to differentiate into a specific tissue withdraw from the cell cycle and start a process of tissue maturation that involves up-regulation of genes specific for the differentiated tissue and down-regulation of genes specific for progenitor cells (1, 2). This developmentally regulated process culminates in formation of compact blocks of heterochromatin inside the nuclei and spatial segregation of heterochromatin and euchromatin domains (3). Chromatin condensation prevents certain transcription factors from activating genes in the compact chromatin (4). Recent studies suggest that each tissue type has its own unique program that orchestrates tissue maturation, with specific sets of chromatin architectural and remodeling proteins, histone modifications, and micro-RNA (5-12).The mammalian retina is a part of the CNS and is derived from the optic cup, an outgrowth of forebrain neuroepithelium formed early in CNS development. Six major neuronal and one glial cell types are generated from the multipotential retinal progenitors in a stereotypic temporal sequence. In mice the terminal differentiation of retinal cells spans from embryonic day ...

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Chromatin condensation via the condensin II complex is required for peripheral T-cell quiescence

Cited by 131 publications

References 58 publications

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

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

Condensins: universal organizers of chromosomes with diverse functions

Developmentally Regulated Linker Histone H1c Promotes Heterochromatin Condensation and Mediates Structural Integrity of Rod Photoreceptors in Mouse Retina

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