X-chromosome inactivation: new insights into cis and trans regulation

Galupa, Rafael; Heard, Edith

doi:10.1016/j.gde.2015.04.002

Cited by 141 publications

(145 citation statements)

References 74 publications

(83 reference statements)

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“…These observations suggest that Xi was not only more compact (36) but also adopted a spatially more intermixed chromatin arrangement with more homogeneous inter-loci distances, reminiscent of the chromatin organization observed for Polycomb-repressed domains using super-resolution imaging (13). Given the enrichment of Polycomb group proteins on Xi (33,34), these observations suggest a potentially general mechanism to induce such a compact and highly intermixed chromatin folding configuration.…”

mentioning

confidence: 71%

“…We imaged 40 TADs (out of 86 total), spanning the whole chromosome at relatively uniform intervals. It is known that one of the two copies of ChrX in female mammalian cells undergoes X-inactivation (33,34). We used TAD coordinates obtained from the combined Hi-C data (8) of both active and inactive copies of ChrX (Xa and Xi) to determine labeling sites but note that the TAD structures are attenuated or absent on Xi (9, 35).…”

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confidence: 99%

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Spatial Organization of Chromatin Domains and Compartments in Single Chromosomes

Wang

Beliveau

et al. 2017

Biophysical Journal

203

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The spatial organization of chromatin critically impacts genome function. Recent chromosomeconformation-capture studies have revealed topologically-associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized fashion in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.The spatial organization of chromatin, such as chromatin domains, chromatin loops, associations of chromatin with nuclear structures, and chromosome territories, plays an important role in essential genome functions (1-6). However, many gaps remain in our understanding of the three-dimensional (3D) folding of individual chromosomes in the nucleus. Recently, chromosome-conformation-capture methods such as Hi-C (4, 7) have revealed a wealth of structural insights for interphase chromosomes. For example, chromatin is organized into topologically-associating domains (TADs) or contact domains that are hundreds of kilobases (kb) in size (8-11). These domains tend to spatially segregate from each other (9, 12, 13) and, in Drosophila, correspond to the banding patterns of polytene chromosomes (14, 15). At length scales from several hundred kilobases to several megabases, the power-law scaling of Hi-C contact frequency is consistent with a fractalglobule polymer model (7, 16), whereas, within TADs, Hi-C contact maps are better

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confidence: 71%

mentioning

confidence: 99%

Spatial Organization of Chromatin Domains and Compartments in Single Chromosomes

Wang

Beliveau

et al. 2017

Biophysical Journal

203

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“…These sites are then recruited to the nuclear lamina, effectively bringing another set of active genes (yellow regions) into closer contact with the Xist transcription locus (right panel). Because the Xist transcription locus escapes Xist coating and silencing, it is positioned away from the nuclear lamina (7,8,5,2,1) and therefore will be close to sites that have not yet been coated and silenced by Xist. This iterative process would enable Xist to spread to, and silence, actively transcribed genes across the entire X-chromosome.…”

Section: Fig S6 δRs-lbr and δTm-lbr Localize Properly In The Nucleamentioning

confidence: 99%

Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing

Chen

Blanco

Jackson

et al. 2016

Science

243

210

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Plunging into a domain of silence Female mammals have two X chromosomes. One must be silenced to “balance” gene dosage with male XY cells. The Xist long noncoding RNA coats the inactive X chromosome in female mammalian cells. Chen et al. show that the Xist RNA helps recruit the X chromosome to the internal rim of the cell nucleus, a region where gene expression is silenced. Xist is recruited to the domain through an interaction with the Lamin B receptor. This recruitment allows the Xist RNA to spread across the future inactive X chromosome, shutting down gene expression. Science , this issue p. 468

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“…Taken together, these data strongly suggest that asDOG1 acts in cis in seed dormancy control. Examples of cis-acting antisense mechanisms include Xist-mediated allele-specific X-chromosome inactivation in humans and PHO gene regulation in yeast (54,55). In addition, it has been suggested that in plants the antisense transcript COOLAIR acts via the process of its transcription or by formation of an RNA cloud, as seen in single-molecule FISH suppressing FLC transcription in cis (22,32).…”

Section: Dog1 Antisense Is a Suppressor Of Seed Dormancy In Arabidopsismentioning

confidence: 99%

Control of seed dormancy in Arabidopsis by a cis -acting noncoding antisense transcript

Fedak

Palusińska

Krzyczmonik

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

119

168

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Seed dormancy is one of the most crucial process transitions in a plant's life cycle. Its timing is tightly controlled by the expression level of the Delay of Germination 1 gene (DOG1). DOG1 is the major quantitative trait locus for seed dormancy in Arabidopsis and has been shown to control dormancy in many other plant species. This is reflected by the evolutionary conservation of the functional short alternatively polyadenylated form of the DOG1 mRNA. Notably, the 3′ region of DOG1, including the last exon that is not included in this transcript isoform, shows a high level of conservation at the DNA level, but the encoded polypeptide is poorly conserved. Here, we demonstrate that this region of DOG1 contains a promoter for the transcription of a noncoding antisense RNA, asDOG1, that is 5′ capped, polyadenylated, and relatively stable. This promoter is autonomous and asDOG1 has an expression profile that is different from known DOG1 transcripts. Using several approaches we show that asDOG1 strongly suppresses DOG1 expression during seed maturation in cis, but is unable to do so in trans. Therefore, the negative regulation of seed dormancy by asDOG1 in cis results in allele-specific suppression of DOG1 expression and promotes germination. Given the evolutionary conservation of the asDOG1 promoter, we propose that this cis-constrained noncoding RNA-mediated mechanism limiting the duration of seed dormancy functions across the Brassicaceae.seed dormancy | DOG1 gene | cis-acting ncRNA | antisense transcript P lants have evolved elaborate adaptation mechanisms to cope with unexpected and rapid changes in their natural environment (1). The division of the plant life cycle into consecutive developmental phases can be viewed as one such mechanism. This compartmentalization allows plants to focus their resources on particular tasks. The most pronounced developmental phases in plant development are seed dormancy, the juvenile phase, vegetative growth, flowering, and senescence (2). The transition between each successive phase has to be tightly controlled and aligned with the plant's internal metabolic state and external conditions.Seeds are characterized by their remarkable ability to withstand harsh environmental conditions (3). This is in part because of a seed dormancy mechanism that imposes a block on the ability of seeds to sense permissive conditions and initiate germination (4, 5). This mechanism allows seeds to temporarily bypass favorable conditions to germinate in an environment that will support the entire plant life cycle. Seed dormancy is under strong evolutionary selection because the improper timing of germination often results in immediate death (6). In addition, from an agronomical point of view, seed dormancy has been a subject of intensive selection, because on the one hand strong dormancy leads to uneven germination, but on the other hand weak dormancy may result in preharvest sprouting because of germination on the mother plant (7).An analysis of seed dormancy variability among Arabidopsis thaliana ac...

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X-chromosome inactivation: new insights into cis and trans regulation

Cited by 141 publications

References 74 publications

Spatial Organization of Chromatin Domains and Compartments in Single Chromosomes

Spatial Organization of Chromatin Domains and Compartments in Single Chromosomes

Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing

Control of seed dormancy in Arabidopsis by a cis -acting noncoding antisense transcript

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