On TADs and LADs: Spatial Control Over Gene Expression

Gonzalez‐Sandoval, Adriana; Gasser, Susan M.

doi:10.1016/j.tig.2016.05.004

Cited by 164 publications

(125 citation statements)

References 71 publications

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“…Use of the CRISPR-Cas9 system allows an effective dissection of regulatory mechanisms at the DNA level including complex enhancers [100]. A major gap exists in our understanding of the posttranscriptional, translational, and posttranslational regulatory mechanisms functioning in the lens [241–243], as well as numerous cross-talks occuring between individual signal transduction pathways [221, 244], nuclear organization [245, 246], and how noncoding RNAs regulate nuclear organization and gene expression [247]. Ongoing studies are focused on lens chromatin dynamics by ATAC-seq, identification of lncRNAs and microRNAs and their lens functions.…”

Section: Discussionmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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Ocular lens development represents an advantageous system to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and underlying gene regulatory networks. Spatiotemporaly regulated domains of BMP, FGF, and other signaling molecules in the late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens and optic cup morphogenesis. Pax6, c-Maf, Hsf4, Prox1, Sox1, and a few additional factors regulate expression of the lens structural proteins, the crystallins. A multitude of cross-talks between a diverse array of signaling pathways control the complexity and order of the lens morphogenetic processes and its transparency.

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Section: Discussionmentioning

confidence: 99%

Signaling and Gene Regulatory Networks in Mammalian Lens Development

2017

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“…Our studies provide evidence to the growing body of literature which reinforce the role of nucleoporins in regulating chromatin organization and gene expression. Gene expression regulation is typically accompanied by an altered occupancy of active and inactive histone marks on gene promoters [66, 67]. The active state of the HOXA gene cluster is marked by active histone marks such as H3K9ac and H3K4me3, while the inactive state shows an enrichment of inactive marks such as H3K9me3 and H3K27me3 [36, 66, 68].…”

Section: Discussionmentioning

confidence: 99%

HOXA repression is mediated by nucleoporin Nup93 assisted by its interactors Nup188 and Nup205

Labade

Karmodiya

Sengupta

2016

Epigenetics & Chromatin

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BackgroundThe nuclear pore complex (NPC) mediates nuclear transport of RNA and proteins into and out of the nucleus. Certain nucleoporins have additional functions in chromatin organization and transcription regulation. Nup93 is a scaffold nucleoporin at the nuclear pore complex which is associated with human chromosomes 5, 7 and 16 and with the promoters of the HOXA gene as revealed by ChIP-on-chip studies using tiling microarrays for these chromosomes. However, the functional consequences of the association of Nup93 with HOXA is unknown.ResultsHere, we examined the association of Nup93 with the HOXA gene cluster and its consequences on HOXA gene expression in diploid colorectal cancer cells (DLD1). Nup93 showed a specific enrichment ~1 Kb upstream of the transcription start site of each of the HOXA1, HOXA3 and HOXA5 promoters, respectively. Furthermore, the association of Nup93 with HOXA was assisted by its interacting partners Nup188 and Nup205. The depletion of the Nup93 sub-complex significantly upregulated HOXA gene expression levels. However, expression levels of a control gene locus (GLCCI1) on human chromosome 7 were unaffected. Three-dimensional fluorescence in situ hybridization (3D-FISH) analyses revealed that the depletion of the Nup93 sub-complex (but not Nup98) disengages the HOXA gene locus from the nuclear periphery, suggesting a potential role for Nup93 in tethering and repressing the HOXA gene cluster. Consistently, Nup93 knockdown increased active histone marks (H3K9ac), decreased repressive histone marks (H3K27me3) on the HOXA1 promoter and increased transcription elongation marks (H3K36me3) within the HOXA1 gene. Moreover, the combined depletion of Nup93 and CTCF (a known organizer of HOXA gene cluster) but not Nup93 alone, significantly increased GLCCI1 gene expression levels. Taken together, this suggests a novel role for Nup93 and its interactors in repressing the HOXA gene cluster.ConclusionsThis study reveals that the nucleoporin Nup93 assisted by its interactors Nup188 and Nup205 mediates the repression of HOXA gene expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-016-0106-0) contains supplementary material, which is available to authorized users.

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“…In the case of transcription factors, the presence of DNA methylation can alter their cognate motif and therefore affect where they bind 222–223 . Cumulatively, these modifications affect the overall compaction and packaging of DNA around histones, which alter the ability of transcriptional machinery to bind DNA 224 . Additional layers of gene regulation are provided by the packaging of chromatin, which is regulated by histone occupancy and can either facilitate or block transcription factor binding and the initiation of transcription, and the association of DNA into topologically associated domains in which regions of DNA are tethered together spatially 224,225 .…”

Section: Figmentioning

confidence: 99%

Intrinsic mechanisms of neuronal axon regeneration

2018

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Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs. Although many questions remain about the interplay between these mechanisms, these new findings provide important insights into the pivotal role of coordinated gene expression and chromatin remodelling in the neuronal response to injury.

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On TADs and LADs: Spatial Control Over Gene Expression

Cited by 164 publications

References 71 publications

Signaling and Gene Regulatory Networks in Mammalian Lens Development

Signaling and Gene Regulatory Networks in Mammalian Lens Development

HOXA repression is mediated by nucleoporin Nup93 assisted by its interactors Nup188 and Nup205

Intrinsic mechanisms of neuronal axon regeneration

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