Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins

Harr, Jennifer C.; Luperchio, Teresa Romeo; Wong, Xianrong; Cohen, Erez; Wheelan, Sarah J.; Reddy, Karen L.

doi:10.1083/jcb.201405110

Cited by 277 publications

(429 citation statements)

References 105 publications

(196 reference statements)

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“…vLAD borders appear to be critical for their dynamic association with the lamina, and are enriched for YY1 binding sites [74]. That YY1 plays a role in this process agrees with previous studies demonstrating the recruitment of PRC2 by YY1 [75][76][77][78][79][80][81][82].…”

Section: How Modulators Of Chromatin State and Organization Might Keesupporting

confidence: 90%

“…That YY1 plays a role in this process agrees with previous studies demonstrating the recruitment of PRC2 by YY1 [75][76][77][78][79][80][81][82]. Accordingly, chromatin repositioning to the nuclear lamina is dependent on YY1 and H3K27me3 enrichment at LADs, in addition to H3K9me2/3 [74,[83][84][85].…”

Section: How Modulators Of Chromatin State and Organization Might Keesupporting

confidence: 90%

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Spatial Organization of Epigenomes

2016

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The role of genome architecture in transcription regulation has become the focus of an increasing number of studies over the past decade. Chromatin organization can have a significant impact on gene expression by promoting or restricting the physical proximity between regulatory DNA elements. Given that any change in chromatin state has the potential to alter DNA folding and the proximity between control elements, the spatial organization of chromatin is inherently linked to its molecular composition. In this review, we explore how modulators of chromatin state and organization might keep gene expression in check. We discuss recent findings and present some of the less well-studied aspects of spatial genome organization such as chromatin dynamics and regulation by non-coding RNAs.

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Section: How Modulators Of Chromatin State and Organization Might Keesupporting

confidence: 90%

Section: How Modulators Of Chromatin State and Organization Might Keesupporting

confidence: 90%

Spatial Organization of Epigenomes

2016

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“…Depletion of repressive chromatin modifications enriched in LADs such as H3K9me2/3 results in disrupted lamina association (Zullo et al 2012;Bian et al 2013;Demmerle et al 2013;Kind et al 2013;Harr et al 2015), suggesting that the marks not only provide for silencing but also themselves contribute to locus affinity for the periphery. At the same time, specific nuclear envelope proteins are important for peripheral tethering of endogenous developmentally repositioning loci (Zullo et al 2012;Solovei et al 2013;Robson et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Log 2 (Lamin B1-Dam/Dam-only) ratios were generated and used to identify LADs in resting and activated Jurkat T cells based on a circular binary segmentation algorithm slightly modified from that previously described (see Methods) (Harr et al 2015). LADs were mapped onto the hg19 assembly because hg19 was used for earlier data sets used for comparison, but all regions examined by fluorescence in situ hybridization (FISH; see below) were confirmed to be unaltered in the newer hg38 assembly.…”

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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“…48,49 More recently, mammalian Lamina associating sequences (LAS) binding several transcriptional repressors target different loci to the nuclear lamina for repression. 50,51 In C. elegans, heat shock-induced promoters were shown to be recruited to nuclear pores in a similar manner as yeast GRS. 46 Prime candidates for X-specific sequences that may direct male-specific targeting of the chromosome to the nuclear periphery are rex sites.…”

Section: The Male X Chromosome Demonstrates a Spatial Preference For mentioning

confidence: 99%

Linking dosage compensation and X chromosome nuclear organization inC. elegans

Sharma

Meister

2015

Nucleus

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A nimal sex is determined by the number of X chromosomes in many species, creating unequal gene dosage (aneuploidy) between sexes. Dosage Compensation mechanisms equalize this dosage difference by regulating X-linked gene expression. In the nematode C. elegans the current model suggests that DC is achieved by a 2-fold transcriptional downregulation in hermaphrodites mediated by the Dosage Compensation Complex (DCC), which restricts access to RNA Polymerase II by an unknown mechanism. Taking a nuclear organization point of view, we showed that the male X chromosome resides in the pore proximal subnuclear compartment whereas the DCC bound to the X, inhibits this spatial organization in the hermaphrodites. Here we discuss our results and propose a model that reassigns the role of DCC from repression of genes to inhibition of activation.

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Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins

Abstract: Localization of specific chromatin domains to the nuclear lamina is mediated by YY1 and lamin A/C and is dependent on a specific histone modification profile.

Cited by 277 publications

References 105 publications

Spatial Organization of Epigenomes

Spatial Organization of Epigenomes

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

Linking dosage compensation and X chromosome nuclear organization inC. elegans

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