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XCI AND Xist

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https://www.readbyqxmd.com/read/29861859/epigenetic-reprogramming-by-na%C3%A3-ve-conditions-establishes-an-irreversible-state-of-partial-x-chromosome-reactivation-in-female-stem-cells
#1
Alexandra V Panova, Alexandra N Bogomazova, Maria A Lagarkova, Sergey L Kiselev
Female human pluripotent stem cells (PSCs) have variable X-chromosome inactivation (XCI) status. One of the X chromosomes may either be inactive (Xi) or display some active state markers. Long-term cultivation of PSCs may lead to an erosion of XCI and partial X reactivation. Such heterogeneity and instability of XCI status might hamper the application of human female PSCs for therapy or disease modeling. We attempted to address XCI heterogeneity by reprogramming human embryonic stem cells (hESCs) to the naïve state...
May 18, 2018: Oncotarget
https://www.readbyqxmd.com/read/29848858/-new-approach-to-the-investigation-of-dohad-using-x-inactivation-gene-expression-system
#2
Takayuki Kumamoto, Shigeru Oshio
X-chromosome inactivation (XCI) occurs during the gestation period to compensate for the dosage of X-linked genes in female mammals. Xist RNA is a long noncoding RNA with a global epigenetic function and is indispensable for XCI from the initiation to establishment and maintenance phases. The X chromosome contains over 1,000 genes that are essential for proper development, especially that of the brain, immune system, metabolism and reproductive functions. We found that exposure to bisphenol A or folate deficiency during the fetal period changes the expressions of Xist, Tsix (the antisense repressor of Xist), and many X chromosome linked genes widely in newborn mice...
2018: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
https://www.readbyqxmd.com/read/29804891/exit-from-naive-pluripotency-induces-a-transient-x-chromosome-inactivation-like-state-in-males
#3
Elsa J Sousa, Hannah T Stuart, Lawrence E Bates, Mohammadmersad Ghorbani, Jennifer Nichols, Sabine Dietmann, José C R Silva
A hallmark of naive pluripotency is the presence of two active X chromosomes in females. It is not clear whether prevention of X chromosome inactivation (XCI) is mediated by gene networks that preserve the naive state. Here, we show that robust naive pluripotent stem cell (nPSC) self-renewal represses expression of Xist, the master regulator of XCI. We found that nPSCs accumulate Xist on the male X chromosome and on both female X chromosomes as they become NANOG negative at the onset of differentiation. This is accompanied by the appearance of a repressive chromatin signature and partial X-linked gene silencing, suggesting a transient and rapid XCI-like state in male nPSCs...
May 16, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29706539/the-ftx-noncoding-locus-controls-x-chromosome-inactivation-independently-of-its-rna-products
#4
Giulia Furlan, Nancy Gutierrez Hernandez, Christophe Huret, Rafael Galupa, Joke Gerarda van Bemmel, Antonio Romito, Edith Heard, Céline Morey, Claire Rougeulle
Accumulation of the Xist long noncoding RNA (lncRNA) on one X chromosome is the trigger for X chromosome inactivation (XCI) in female mammals. Xist expression, which needs to be tightly controlled, involves a cis-acting region, the X-inactivation center (Xic), containing many lncRNA genes that evolved concomitantly to Xist from protein-coding ancestors through pseudogeneization and loss of coding potential. Here, we uncover an essential role for the Xic-linked noncoding gene Ftx in the regulation of Xist expression...
April 20, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29546464/chromosome-wide-gene-dosage-rebalance-may-benefit-tumor-progression
#5
Honglei Zhang, Xing Yang, Xu Feng, Haibo Xu, Qin Yang, Li Zou, Mei Yan, Dequan Liu, Xiaosan Su, Baowei Jiao
The high-risk of tumor initiation in patients with Turner syndrome (TS) characterized by X chromosome monosomy in women has been well established and aneuploidy, defined as an abnormal number of chromosomes, is a common feature in human cancer. However, the underlying mechanisms of X chromosome aneuploidy promoting tumorigenesis remain obscure. We propose that chromosome-wide gene dosage imbalance (CDI) may serve as an important mechanism. Here, we assess the relative expression ratios of X chromosome and autosomes (expression ratios of X:AA) between tumor samples and adjacent normal samples across 16 tumor types using expression datasets from The Cancer Genome Atlas (TCGA) project...
March 15, 2018: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/29353144/effects-of-the-hdac-inhibitor-scriptaid-on-the-in-vitro-development-of-bovine-embryos-and-on-imprinting-gene-expression-levels
#6
R Laguna-Barraza, M J Sánchez-Calabuig, A Gutiérrez-Adán, D Rizos, S Pérez-Cerezales
This study examines the effects of the histone deacetylation inhibitor scriptaid (SCR) on preimplantation embryo development in vitro and on imprinting gene expression. We hypothesized that SCR would increase histone acetylation levels, enhance embryonic genome activation, and regulate imprinting and X-chromosome inactivation (XCI) in in vitro produced bovine embryos. Zygotes were cultured in vitro in presence or absence of SCR added at different time points. We assessed cleavage and blastocyst rates as well as the quality of blastocysts through: (i) differential cell counts; (ii) survival after vitrification/thawing and (iii) gene expression analysis -including imprinted genes...
April 1, 2018: Theriogenology
https://www.readbyqxmd.com/read/29316023/sj%C3%A3-gren-s-syndrome-x-chromosome-dose-effect-an-epigenetic-perspective
#7
REVIEW
J-Lc Mougeot, B D Noll, F K Bahrani Mougeot
Sjögren's syndrome (SS) is a chronic autoimmune disease affecting exocrine glands leading to mouth and eyes dryness. The extent to which epigenetic DNA methylation changes are responsible for an X-chromosome dose effect has yet to be determined. Our objectives were to (i) describe how epigenetic DNA methylation changes could explain an X-chromosome dose effect in SS for women with normal 46,XX genotype and (ii) determine the relevant relationships to this dose effect, between X-linked genes, genes controlling X-chromosome inactivation (XCI) and genes encoding associated transcription factors, all of which are differentially expressed and/or differentially methylated in the salivary glands of patients with SS...
January 9, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29281819/rlim-dependent-and-independent-pathways-for-x-chromosome-inactivation-in-female-escs
#8
Feng Wang, Kurtis N McCannell, Ana Bošković, Xiaochun Zhu, JongDae Shin, Jun Yu, Judith Gallant, Meg Byron, Jeanne B Lawrence, Lihua J Zhu, Stephen N Jones, Oliver J Rando, Thomas G Fazzio, Ingolf Bach
During female mouse embryogenesis, two forms of X chromosome inactivation (XCI) ensure dosage compensation from sex chromosomes. Beginning at the four-cell stage, imprinted XCI (iXCI) exclusively silences the paternal X (Xp), and this pattern is maintained in extraembryonic cell types. Epiblast cells, which give rise to the embryo proper, reactivate the Xp (XCR) and undergo a random form of XCI (rXCI) around implantation. Both iXCI and rXCI depend on the long non-coding RNA Xist. The ubiquitin ligase RLIM is required for iXCI in vivo and occupies a central role in current models of rXCI...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29089420/genomic-imprinting-of-xist-by-maternal-h3k27me3
#9
Azusa Inoue, Lan Jiang, Falong Lu, Yi Zhang
Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X-chromosome inactivation (XCI) in female mammals. However, the mechanism underlying Xist imprinting is unclear. Here we show that the Xist locus is coated with a broad H3K27me3 domain that is established during oocyte growth and persists through preimplantation development in mice. Loss of maternal H3K27me3 induces maternal Xist expression and maternal XCI in preimplantation embryos. Our study thus identifies maternal H3K27me3 as the imprinting mark of Xist ...
October 1, 2017: Genes & Development
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
#10
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 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
#11
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
#12
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
#13
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
#14
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...
December 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
#15
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
#16
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
#17
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
#18
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
#19
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)...
June 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
#20
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
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