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XCI AND Xist

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https://www.readbyqxmd.com/read/28991910/loss-of-xist-rna-from-the-inactive-x-during-b-cell-development-is-restored-in-a-dynamic-yy1-dependent-two-step-process-in-activated-b-cells
#1
Camille M Syrett, Vishal Sindhava, Suchita Hodawadekar, Arpita Myles, Guanxiang Liang, Yue Zhang, Satabdi Nandi, Michael Cancro, Michael Atchison, Montserrat C Anguera
X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradually lost during B cell development. Activation of mature B cells restores Xist RNA and heterochromatin to the Xi in a dynamic two-step process that differs in timing and pattern, depending on the method of B cell stimulation...
October 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28947658/x-chromosome-inactivation-in-a-female-carrier-of-a-1-28-mb-deletion-encompassing-the-human-x-inactivation-centre
#2
B de Hoon, Erik Splinter, B Eussen, J C W Douben, E Rentmeester, M van de Heijning, J S E Laven, J E M M de Klein, J Liebelt, J Gribnau
X chromosome inactivation (XCI) is a mechanism specifically initiated in female cells to silence one X chromosome, thereby equalizing the dose of X-linked gene products between male and female cells. XCI is regulated by a locus on the X chromosome termed the X-inactivation centre (XIC). Located within the XIC is XIST, which acts as a master regulator of XCI. During XCI, XIST is upregulated on the inactive X chromosome and chromosome-wide cis spreading of XIST leads to inactivation. In mouse, the Xic comprises Xist and all cis-regulatory elements and genes involved in Xist regulation...
November 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28947657/human-x-chromosome-inactivation-and-reactivation-implications-for-cell-reprogramming-and-disease
#3
REVIEW
Irene Cantone, Amanda G Fisher
X-chromosome inactivation (XCI) is an exemplar of epigenetic regulation that is set up as pluripotent cells differentiate. Once established, XCI is stably propagated, but can be reversed in vivo or by pluripotent reprogramming in vitro Although reprogramming provides a useful model for inactive X (Xi) reactivation in mouse, the relative instability and heterogeneity of human embryonic stem (ES) cells and induced pluripotent stem cells hampers comparable progress in human. Here we review studies aimed at reactivating the human Xi using different reprogramming strategies...
November 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28947655/mechanistic-insights-in-x-chromosome-inactivation
#4
REVIEW
Zhipeng Lu, Ava C Carter, Howard Y Chang
X-chromosome inactivation (XCI) is a critical epigenetic mechanism for balancing gene dosage between XY males and XX females in eutherian mammals. A long non-coding RNA (lncRNA), XIST, and its associated proteins orchestrate this multi-step process, resulting in the inheritable silencing of one of the two X-chromosomes in females. The XIST RNA is large and complex, exemplifying the unique challenges associated with the structural and functional analysis of lncRNAs. Recent technological advances in the analysis of macromolecular structure and interactions have enabled us to systematically dissect the XIST ribonucleoprotein complex, which is larger than the ribosome, and its place of action, the inactive X-chromosome...
November 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28766050/unique-xci-evolution-in-tokudaia-initial-xci-of-the-neo-x-chromosome-in-tokudaia-muenninki-and-function-loss-of-xist-in-tokudaia-osimensis
#5
Hideki Zushi, Chie Murata, Shusei Mizushima, Chizuko Nishida, Asato Kuroiwa
X chromosome inactivation (XCI) is an essential mechanism to compensate gene dosage in mammals. Here, we show that XCI has evolved differently in two species of the genus Tokudaia. The Amami spiny rat, Tokudaia osimensis, has a single X chromosome in males and females (XO/XO). By contrast, the Okinawa spiny rat, Tokudaia muenninki, has XX/XY sex chromosomes like most mammals, although the X chromosome has acquired a neo-X region by fusion with an autosome. BAC clones containing the XIST gene, which produces the long non-coding RNA XIST required for XCI, were obtained by screening of T...
August 2, 2017: Chromosoma
https://www.readbyqxmd.com/read/28686623/xist-rna-repeat-e-is-essential-for-ash2l-recruitment-to-the-inactive-x-and-regulates-histone-modifications-and-escape-gene-expression
#6
Minghui Yue, Akiyo Ogawa, Norishige Yamada, John Lalith Charles Richard, Artem Barski, Yuya Ogawa
Long non-coding RNA Xist plays a crucial role in establishing and maintaining X-chromosome inactivation (XCI) which is a paradigm of long non-coding RNA-mediated gene regulation. Xist has Xist-specific repeat elements A-F which are conserved among eutherian mammals, underscoring their functional importance. Here we report that Xist RNA repeat E, a conserved Xist repeat element in the Xist exon 7, interacts with ASH2L and contributes to maintenance of escape gene expression level on the inactive X-chromosome (Xi) during XCI...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28663000/skewed-x-chromosome-inactivation-and-xist-locus-methylation-levels-do-not-contribute-to-the-lower-prevalence-of-parkinson-s-disease-in-females
#7
Amit Sharma, Oliver Kaut, Anna Pavlova, Holger Fröhlich, Ashar Ahmad, Ina Schmitt, Osman El-Maarri, Johannes Oldenburg, Ullrich Wüllner
Parkinson's disease (PD) is a degenerative disorder of the nervous system and the cause of the majority of sporadic cases is unknown. Females are relatively protected from PD as compared with males and linkage studies suggested a PD susceptibility locus on the X chromosome. To determine a putative association of skewed X-chromosome inactivation (XCI) and PD, we examined XCI patterns using a human androgen receptor gene-based assay (HUMARA) and did not identify any association of skewed or random X inactivation with clinical heterogeneity among female PD patients...
September 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28408975/x-chromosome-inactivation-new-players-in-the-initiation-of-gene-silencing
#8
REVIEW
Ines Pinheiro, Edith Heard
X chromosome inactivation (XCI) is a dosage compensation process that was adopted by female mammals to balance gene dosage between XX females and XY males. XCI starts with the upregulation of the non-coding RNA Xist, after which most X-linked genes are silenced and acquire a repressive chromatin state. Even though the chromatin marks of the inactive X have been fairly well described, the mechanisms responsible for the initiation of XCI remain largely unknown. In this review, we discuss recent developments that revealed unexpected factors playing a role in XCI and that might be of crucial importance to understand the mechanisms responsible for the very first steps of this chromosome-wide gene-silencing event...
2017: F1000Research
https://www.readbyqxmd.com/read/28401797/the-state-of-skewed-x-chromosome-inactivation-is-retained-in-the-induced-pluripotent-stem-cells-from-a-female-with-hemophilia-b
#9
Cuicui Lyu, Jun Shen, Jianping Zhang, Feng Xue, Xiaofan Liu, Wei Liu, Rongfeng Fu, Liyan Zhang, Huiyuan Li, Donglei Zhang, Xiaobing Zhang, Tao Cheng, Renchi Yang, Lei Zhang
Skewed X chromosome inactivation (XCI) is a rare reason for hemophilia B in females. It is indefinite whether X chromosome reactivation (XCR) would occur when cells of hemophilia B patients with skewed XCI were reprogrammed into induced pluripotent stem cells (iPSCs). In this study, we investigated a female hemophilia B patient with a known F9 gene mutation: c.676C>T, p.Arg226Trp. We demonstrated that skewed XCI was the pathogenesis of the patient, and we successfully generated numerous iPSC colonies of the patient from peripheral blood mononuclear cells (PBMNCs), which was the first time for generating hemophilia-specific iPSCs from PBMNCs...
July 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28387970/mutation-of-the-xist-gene-upregulates-expression-of-x-linked-genes-but-decreases-the-developmental-rates-of-cloned-male-porcine-embryos
#10
Yang Yang, Dan Wu, Dewu Liu, Junsong Shi, Rong Zhou, Xiaoyan He, Jianping Quan, Gengyuan Cai, Enqin Zheng, Zhenfang Wu, Zicong Li
XIST is an X-linked, non-coding gene responsible for the cis induction of X-chromosome inactivation (XCI). Knockout of the XIST allele on an active X chromosome abolishes erroneous XCI and enhances the in vivo development of cloned mouse embryos by more than 10-fold. This study aimed to investigate whether a similar manipulation would improve cloning efficiency in pigs. A male, porcine kidney cell line containing an EGFP insert in exon 1 of the XIST gene, resulting in a knockout allele (XIST-KO), was generated by homologous recombination using transcription activator-like effector nucleases (TALENs)...
April 7, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28368037/high-resolution-rna-allelotyping-along-the-inactive-x-chromosome-evidence-of-rna-polymerase-iii-in-regulating-chromatin-configuration
#11
Ru Hong, Bingqing Lin, Xinyi Lu, Lan-Tian Lai, Xin Chen, Amartya Sanyal, Huck-Hui Ng, Kun Zhang, Li-Feng Zhang
We carried out padlock capture, a high-resolution RNA allelotyping method, to study X chromosome inactivation (XCI). We examined the gene reactivation pattern along the inactive X (Xi), after Xist (X-inactive specific transcript), a prototype long non-coding RNA essential for establishing X chromosome inactivation (XCI) in early embryos, is conditionally deleted from Xi in somatic cells (Xi(∆Xist)). We also monitored the behaviors of X-linked non-coding transcripts before and after XCI. In each mutant cell line, gene reactivation occurs to ~6% genes along Xi(∆Xist) in a recognizable pattern...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257137/novel-players-in-x-inactivation-insights-into-xist-mediated-gene-silencing-and-chromosome-conformation
#12
REVIEW
Simão T da Rocha, Edith Heard
The nuclear long noncoding RNA (lncRNA) Xist ensures X-chromosome inactivation (XCI) in female placental mammals. Although Xist is one of the most intensively studied lncRNAs, the mechanisms associated with its capacity to trigger chromosome-wide gene silencing, the formation of facultative heterochromatin and an unusual 3D conformation of the inactive X chromosome (Xi) have remained elusive. Now researchers have identified novel functional partners of Xist in a series of breakthrough studies, using unbiased techniques to isolate Xist-bound proteins, as well as forward genetic screens...
March 3, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28236732/x-chromosome-inactivation-silencing-topology-and-reactivation
#13
REVIEW
Teresa Robert Finestra, Joost Gribnau
To ensure X-linked gene dosage compensation between females (XX) and males (XY), one X chromosome undergoes X chromosome inactivation (XCI) in female cells. This process is tightly regulated throughout development by many different factors, with Xist as a key regulator, encoding a long non-coding RNA, involved in establishment of several layers of repressive epigenetic modifications. Several recent studies on XCI focusing on identification and characterization of Xist RNA-protein interactors, revealed new factors involved in gene silencing, genome topology and nuclear membrane attachment, amongst others...
February 21, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/27716834/round-spermatid-injection-rescues-female-lethality-of-a-paternally-inherited-xist-deletion-in-mouse
#14
Federica Federici, Aristea Magaraki, Evelyne Wassenaar, Catherina J H van Veen-Buurman, Christine van de Werken, Esther B Baart, Joop S E Laven, J Anton Grootegoed, Joost Gribnau, Willy M Baarends
In mouse female preimplantation embryos, the paternal X chromosome (Xp) is silenced by imprinted X chromosome inactivation (iXCI). This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm) is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist) is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI)...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27542829/female-mice-lacking-xist-rna-show-partial-dosage-compensation-and-survive-to-term
#15
Lin Yang, James E Kirby, Hongjae Sunwoo, Jeannie T Lee
X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal...
August 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27528619/xist-and-tsix-transcription-dynamics-is-regulated-by-the-x-to-autosome-ratio-and-semistable-transcriptional-states
#16
Friedemann Loos, Cheryl Maduro, Agnese Loda, Johannes Lehmann, Gert-Jan Kremers, Derk Ten Berge, J Anton Grootegoed, Joost Gribnau
In female mammals, X chromosome inactivation (XCI) is a key process in the control of gene dosage compensation between X-linked genes and autosomes. Xist and Tsix, two overlapping antisense-transcribed noncoding genes, are central elements of the X inactivation center (Xic) regulating XCI. Xist upregulation results in the coating of the entire X chromosome by Xist RNA in cis, whereas Tsix transcription acts as a negative regulator of Xist Here, we generated Xist and Tsix reporter mouse embryonic stem (ES) cell lines to study the genetic and dynamic regulation of these genes upon differentiation...
November 1, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27504142/thoughts-about-slc16a2-tsix-and-xist-gene-like-sites-in-the-human-genome-and-a-potential-role-in-cellular-chromosome-counting
#17
Martina Rinčić, Ivan Y Iourov, Thomas Liehr
BACKGROUND: Chromosome counting is a process in which cells determine somehow their intrinsic chromosome number(s). The best-studied cellular mechanism that involves chromosome counting is 'chromosome-kissing' and X-chromosome inactivation (XCI) mechanism. It is necessary for the well-known dosage compensation between the genders in mammals to balance the number of active X-chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI, two X-chromosomes are coming in close proximity and pair physically by a specific segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27437574/structural-organization-of-the-inactive-x-chromosome-in-the-mouse
#18
Luca Giorgetti, Bryan R Lajoie, Ava C Carter, Mikael Attia, Ye Zhan, Jin Xu, Chong Jian Chen, Noam Kaplan, Howard Y Chang, Edith Heard, Job Dekker
X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed...
July 28, 2016: Nature
https://www.readbyqxmd.com/read/27262949/the-dynamic-changes-of-x-chromosome-inactivation-during-early-culture-of-human-embryonic-stem-cells
#19
Pingyuan Xie, Qi Ouyang, Lizhi Leng, Liang Hu, Dehua Cheng, Yueqiu Tan, Guangxiu Lu, Ge Lin
X chromosome inactivation (XCI) is required for dosage compensation of X-linked genes in human female cells. Several previous reports have described the promiscuous XCI status in long-term cultured female human embryonic stem cells (hESCs), and the majority of them exhibit non-random XCI. However, when and how such female hESCs acquire the aberrant XCI states during culture is unknown. Herein, through comparing the XCI states in 18 paired hES cell lines throughout early culture, we revealed a uniform dynamic change during this culture period under a widely used culture condition...
July 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27173581/function-and-evolution-of-the-long-noncoding-rna-circuitry-orchestrating-x-chromosome-inactivation-in-mammals
#20
REVIEW
Giulia Furlan, Claire Rougeulle
X-chromosome inactivation (XCI) is a chromosome-wide regulatory process that ensures dosage compensation for X-linked genes in Theria. XCI is established during early embryogenesis and is developmentally regulated. Different XCI strategies exist in mammalian infraclasses and the regulation of this process varies also among closely related species. In Eutheria, initiation of XCI is orchestrated by a cis-acting locus, the X-inactivation center (Xic), which is particularly enriched in genes producing long noncoding RNAs (lncRNAs)...
September 2016: Wiley Interdisciplinary Reviews. RNA
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