Dynamics of transcription-mediated conversion from euchromatin to facultative heterochromatin at the Xist promoter by Tsix

Ohhata, Tatsuya; Yamazawa, Kazuki; Miura-Kamio, Asuka; Takahashi, Saori; Sakai, Satoshi; Tamura, Yuka; Uchida, Chiharu; Kitagawa, Kyoko; Niida, Hiroyuki; Hiratani, Ichiro; Kobayashi, Hisato; Kimurâ, Hiroshi; Wutz, Anton; Kitagawa, Masatoshi

doi:10.1016/j.celrep.2021.108912

Cited by 11 publications

(14 citation statements)

References 67 publications

(64 reference statements)

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“…To validate our NOMe-seq data, we performed MARs-qPCR, a micrococcal nuclease-based method to assess site-specific nucleosome occupancy 87 in differentiating Xmas mESCs for a subset of Smarcc1-responsive or unresponsive promoters. Note that increased MARS-qPCR signal indicates decreased accessibility and is therefore directionally inverse to NoME-seq signal.…”

Section: Resultsmentioning

confidence: 99%

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BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

et al. 2022

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The process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI. Without this action gene silencing fails. Xmas mESCs provide a tractable model for screen-based approaches that enable the discovery of unknown facets of the female-specific process of XCI and epigenetic silencing more broadly.

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Section: Resultsmentioning

confidence: 99%

“…MARS-qPCR was performed as described 87 on Xmas mESCs differentiated for either 4 or 6 days. Primers used for qPCR are listed in Supplementary Data 6 .…”

Section: Methodsmentioning

confidence: 99%

BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

et al. 2022

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“…On the one hand, Suv39h1as triggers H3K4me1 and me2 throughout the locus; on the other, it slightly reduces H3K4me2, H3K4me3, H3K9ac and H3K27ac at the Suv39h1 promoter. Notably, these effects are reminiscent of those associated with the regulation of Xist by its antisense Tsix [29][30][31] , possibly revealing a general property of antisense transcription. While it is possible that the slight increase of euchromatic marks at the Suv39h1 promoter are sufficient to increase the frequency of Suv39h1 transcription, other potential mechanisms cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, Suv39h1as is likely to act as a transcriptional repressor of Suv39h1. To explore this, and given that other antisense transcription units have been shown to modify the chromatin of their corresponding sense gene [29][30][31] , we used a ChIP approach to establish the histone modification profiles of the locus (Fig. 5).…”

Section: Suv39h1asmentioning

confidence: 99%

The activation of a Suv39h1-repressive antisense lncRNA by OCT4 couples the control of H3K9 methylation to pluripotency

Bernard

Dubois

Heurtier

et al. 2021

Preprint

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Histone H3 Lysine 9 (H3K9) methylation, a characteristic mark of heterochromatin, is progressively implemented during development to contribute to cell fate restriction as differentiation proceeds. For instance, in pluripotent mouse Embryonic Stem (ES) cells the global levels of H3K9 methylation are rather low and increase only upon differentiation. Conversely, H3K9 methylation represents an epigenetic barrier for reprogramming somatic cells back to pluripotency. How global H3K9 methylation levels are coupled with the acquisition and loss of pluripotency remains largely unknown. Here, we identify SUV39H1, a major H3K9 di- and tri-methylase, as an indirect target of the pluripotency network of Transcription Factors (TFs). We find that pluripotency TFs, principally OCT4, activate the expression of an uncharacterized antisense long non-coding RNA to Suv39h1, which we name Suv39h1as. In turn, Suv39h1as downregulates Suv39h1 transcription in cis via a mechanism involving the modulation of the chromatin status of the locus. The targeted deletion of the Suv39h1as promoter region triggers increased SUV39H1 expression and H3K9me2 and H3K9me3 levels, leading to accelerated and more efficient commitment into differentiation. We report, therefore, a simple genetic circuitry coupling the global levels of H3K9 methylation to pluripotency in mouse ES cells.

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“…Tsix is in the antisense orientation to Xist and serves to downregulate Xist on the active X [ 33 ]. Additionally, a promoter element of the Linx lncRNA acts as a long-range silencer to influence the choice of X chromosome to be inactivated [ 34 , 35 , 36 ]. The X-linked lncRNA Firre was originally reported to be expressed from both X homologs, but having an allele-specific role on the inactive X by recruiting CTCF and cohesin to maintain perinucleolar positioning of the X-chromosome [ 37 ].…”

Section: Differential Allelic Expression Of Lncrnas In X-inactivationmentioning

confidence: 99%

Differential Allelic Expression among Long Non-Coding RNAs

Heskett

Spellman

Thayer

2021

ncRNA

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Long non-coding RNAs (lncRNA) comprise a diverse group of non-protein-coding RNAs >200 bp in length that are involved in various normal cellular processes and disease states, and can affect coding gene expression through mechanisms in cis or in trans. Since the discovery of the first functional lncRNAs transcribed by RNA Polymerase II, H19 and Xist, many others have been identified and noted for their unusual transcriptional pattern, whereby expression from one chromosome homolog is strongly favored over the other, also known as mono-allelic or differential allelic expression. lncRNAs with differential allelic expression have been observed to play critical roles in developmental gene regulation, chromosome structure, and disease. Here, we will focus on known examples of differential allelic expression of lncRNAs and highlight recent research describing functional lncRNAs expressed from both imprinted and random mono-allelic expression domains.

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Dynamics of transcription-mediated conversion from euchromatin to facultative heterochromatin at the Xist promoter by Tsix

Cited by 11 publications

References 67 publications

BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

The activation of a Suv39h1-repressive antisense lncRNA by OCT4 couples the control of H3K9 methylation to pluripotency

Differential Allelic Expression among Long Non-Coding RNAs

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