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https://www.readbyqxmd.com/read/28939698/the-5-region-of-xist-rna-has-the-potential-to-associate-with-chromatin-through-the-a-repeat
#1
Yuta Chigi, Hiroyuki Sasaki, Takashi Sado
X inactive-specific transcript (Xist) is a long noncoding RNA that plays an essential role in X chromosome inactivation. Although Xist RNA, like common protein-coding mRNAs, is transcribed by RNA polymerase II, spliced and polyadenylated, it is retained in the nucleus and associates with the X chromosome it originates from. It has been assumed that Xist RNA recruits proteins involved in epigenetic modifications and chromatin compaction to the X chromosome. One of the major proteins constituting the nuclear matrix, hnRNP U, has been shown to be required for the association of Xist RNA with the inactive X chromosome (Xi)...
September 22, 2017: RNA
https://www.readbyqxmd.com/read/28923964/repeat-e-anchors-xist-rna-to-the-inactive-x-chromosomal-compartment-through-cdkn1a-interacting-protein-ciz1
#2
Hongjae Sunwoo, David Colognori, John E Froberg, Yesu Jeon, Jeannie T Lee
X chromosome inactivation is an epigenetic dosage compensation mechanism in female mammals driven by the long noncoding RNA, Xist. Although recent genomic and proteomic approaches have provided a more global view of Xist's function, how Xist RNA localizes to the inactive X chromosome (Xi) and spreads in cis remains unclear. Here, we report that the CDKN1-interacting zinc finger protein CIZ1 is critical for localization of Xist RNA to the Xi chromosome territory. Stochastic optical reconstruction microscopy (STORM) shows a tight association of CIZ1 with Xist RNA at the single-molecule level...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28767436/rnai-mediated-knockdown-of-parp1-does-not-improve-the-development-of-female-cloned-mouse-embryos
#3
Guang-Yu Bai, Si-Hang Song, Rui-Zhen Sun, Zi-Hui Zhang, Jingyu Li, Zhen-Dong Wang, Zhong-Hua Liu, Lei Lei
Somatic cell nuclear transfer is an important technique for life science research, but its efficiency is still extremely low, and most genes that are important during early development, such as X chromosome-linked genes, are not appropriately expressed during this process. Poly (ADP-ribose) polymerase (PARP) is an enzyme that transfers ADP ribose clusters to target proteins. PARP family members such as PARP1 participate in cellular signalling pathways through poly (ADP-ribosylation) (PARylation), which ultimately promotes changes in chromatin structure, gene expression, and the localization and activity of proteins that mediate signalling responses...
July 18, 2017: Oncotarget
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
#4
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/28546514/the-nuclear-matrix-protein-ciz1-facilitates-localization-of-xist-rna-to-the-inactive-x-chromosome-territory
#5
Rebeca Ridings-Figueroa, Emma R Stewart, Tatyana B Nesterova, Heather Coker, Greta Pintacuda, Jonathan Godwin, Rose Wilson, Aidan Haslam, Fred Lilley, Renate Ruigrok, Sumia A Bageghni, Ghadeer Albadrani, William Mansfield, Jo-An Roulson, Neil Brockdorff, Justin F X Ainscough, Dawn Coverley
The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder...
May 1, 2017: Genes & 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
#6
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
#7
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
#8
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/28143937/screen-for-reactivation-of-mecp2-on-the-inactive-x-chromosome-identifies-the-bmp-tgf-%C3%AE-superfamily-as-a-regulator-of-xist-expression
#9
Smitha Sripathy, Vid Leko, Robin L Adrianse, Taylor Loe, Eric J Foss, Emily Dalrymple, Uyen Lao, Tonibelle Gatbonton-Schwager, Kelly T Carter, Bernhard Payer, Patrick J Paddison, William M Grady, Jeannie T Lee, Marisa S Bartolomei, Antonio Bedalov
Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding the methyl-CpG-binding protein MeCP2 on the X chromosome. Because restoration of MeCP2 expression in a mouse model reverses neurologic deficits in adult animals, reactivation of the wild-type copy of MeCP2 on the inactive X chromosome (Xi) presents a therapeutic opportunity in RS. To identify genes involved in MeCP2 silencing, we screened a library of 60,000 shRNAs using a cell line with a MeCP2 reporter on the Xi and found 30 genes clustered in seven functional groups...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28118853/allele-specific-analysis-of-cell-fusion-mediated-pluripotent-reprograming-reveals-distinct-and-predictive-susceptibilities-of-human-x-linked-genes-to-reactivation
#10
Irene Cantone, Gopuraja Dharmalingam, Yi-Wah Chan, Anne-Celine Kohler, Boris Lenhard, Matthias Merkenschlager, Amanda G Fisher
BACKGROUND: Inactivation of one X chromosome is established early in female mammalian development and can be reversed in vivo and in vitro when pluripotency factors are re-expressed. The extent of reactivation along the inactive X chromosome (Xi) and the determinants of locus susceptibility are, however, poorly understood. Here we use cell fusion-mediated pluripotent reprograming to study human Xi reactivation and allele-specific single nucleotide polymorphisms (SNPs) to identify reactivated loci...
January 25, 2017: Genome Biology
https://www.readbyqxmd.com/read/27989770/human-naive-pluripotent-stem-cells-model-x-chromosome-dampening-and-x-inactivation
#11
Anna Sahakyan, Rachel Kim, Constantinos Chronis, Shan Sabri, Giancarlo Bonora, Thorold W Theunissen, Edward Kuoy, Justin Langerman, Amander T Clark, Rudolf Jaenisch, Kathrin Plath
Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXa intermediate...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/27989715/human-embryonic-stem-cells-do-not-change-their-x-inactivation-status-during-differentiation
#12
Sanjeet Patel, Giancarlo Bonora, Anna Sahakyan, Rachel Kim, Constantinos Chronis, Justin Langerman, Sorel Fitz-Gibbon, Liudmilla Rubbi, Rhys J P Skelton, Reza Ardehali, Matteo Pellegrini, William E Lowry, Amander T Clark, Kathrin Plath
Applications of embryonic stem cells (ESCs) require faithful chromatin changes during differentiation, but the fate of the X chromosome state in differentiating ESCs is unclear. Female human ESC lines either carry two active X chromosomes (XaXa), an Xa and inactive X chromosome with or without XIST RNA coating (Xi(XIST+)Xa;XiXa), or an Xa and an eroded Xi (XeXa) where the Xi no longer expresses XIST RNA and has partially reactivated. Here, we established XiXa, XeXa, and XaXa ESC lines and followed their X chromosome state during differentiation...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/27507283/ordered-chromatin-changes-and-human-x-chromosome-reactivation-by-cell-fusion-mediated-pluripotent-reprogramming
#13
Irene Cantone, Hakan Bagci, Dirk Dormann, Gopuraja Dharmalingam, Tatyana Nesterova, Neil Brockdorff, Claire Rougeulle, Celine Vallot, Edith Heard, Ronan Chaligne, Matthias Merkenschlager, Amanda G Fisher
Erasure of epigenetic memory is required to convert somatic cells towards pluripotency. Reactivation of the inactive X chromosome (Xi) has been used to model epigenetic reprogramming in mouse, but human studies are hampered by Xi epigenetic instability and difficulties in tracking partially reprogrammed iPSCs. Here we use cell fusion to examine the earliest events in the reprogramming-induced Xi reactivation of human female fibroblasts. We show that a rapid and widespread loss of Xi-associated H3K27me3 and XIST occurs in fused cells and precedes the bi-allelic expression of selected Xi-genes by many heterokaryons (30-50%)...
August 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27437574/structural-organization-of-the-inactive-x-chromosome-in-the-mouse
#14
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/27001848/unusual-maintenance-of-x-chromosome-inactivation-predisposes-female-lymphocytes-for-increased-expression-from-the-inactive-x
#15
Jianle Wang, Camille M Syrett, Marianne C Kramer, Arindam Basu, Michael L Atchison, Montserrat C Anguera
Females have a greater immunological advantage than men, yet they are more prone to autoimmune disorders. The basis for this sex bias lies in the X chromosome, which contains many immunity-related genes. Female mammals use X chromosome inactivation (XCI) to generate a transcriptionally silent inactive X chromosome (Xi) enriched with heterochromatic modifications and XIST/Xist RNA, which equalizes gene expression between the sexes. Here, we examine the maintenance of XCI in lymphocytes from females in mice and humans...
April 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26951653/impaired-imprinted-x-chromosome-inactivation-is-responsible-for-the-skewed-sex-ratio-following-in-vitro-fertilization
#16
Kun Tan, Lei An, Kai Miao, Likun Ren, Zhuocheng Hou, Li Tao, Zhenni Zhang, Xiaodong Wang, Wei Xia, Jinghao Liu, Zhuqing Wang, Guangyin Xi, Shuai Gao, Linlin Sui, De-Sheng Zhu, Shumin Wang, Zhonghong Wu, Ingolf Bach, Dong-Bao Chen, Jianhui Tian
Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns. However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear...
March 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26360551/cancer-testis-antigen-expression-in-serous-endometrial-cancer-with-loss-of-x-chromosome-inactivation
#17
Jun Kang, Hee Jin Lee, Sun-Young Jun, Eun Su Park, Lee-So Maeng
BACKGROUND: Cancer-testis antigens (CTAs) are potential targets for cancer immunotherapy. Many CTAs are located on the X chromosome and are epigenetically regulated. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers and is thought to be related to the overexpression of CTAs. We investigated the relation between expression of CTAs and loss of XCI in endometrial cancer. MATERIALS AND METHODS: We used data generated by The Cancer Genome Atlas Genome Data Analysis Centers and data for Xist knockout mice available at the Gene Expression Omnibus...
2015: PloS One
https://www.readbyqxmd.com/read/26260844/dynamic-interplay-and-function-of-multiple-noncoding-genes-governing-x-chromosome-inactivation
#18
REVIEW
Minghui Yue, John Lalith Charles Richard, Yuya Ogawa
There is increasing evidence for the emergence of long noncoding RNAs (lncRNAs) as important components, especially in the regulation of gene expression. In the event of X chromosome inactivation, robust epigenetic marks are established in a long noncoding Xist RNA-dependent manner, giving rise to a distinct epigenetic landscape on the inactive X chromosome (Xi). The X inactivation center (Xic) is essential for induction of X chromosome inactivation and harbors two topologically associated domains (TADs) to regulate monoallelic Xist expression: one at the noncoding Xist gene and its upstream region, and the other at the antisense Tsix and its upstream region...
January 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26244333/xist-exon-7-contributes-to-the-stable-localization-of-xist-rna-on-the-inactive-x-chromosome
#19
Norishige Yamada, Yuko Hasegawa, Minghui Yue, Tomofumi Hamada, Shinichi Nakagawa, Yuya Ogawa
To equalize X-linked gene dosage between the sexes in mammalian females, Xist RNA inactivates one of the two X-chromosomes. Here, we report the crucial function of Xist exon 7 in X-inactivation. Xist exon 7 is the second-largest exon with a well-conserved repeat E in eutherian mammals, but its role is often overlooked in X-inactivation. Although female ES cells with a targeted truncation of the Xist exon 7 showed no significant differences in their Xist expression levels and RNA stability from control cells expressing wild-type Xist, compromised localization of Xist RNA and incomplete silencing of X-linked genes on the inactive X-chromosome (Xi) were observed in the exon 7-truncated mutant cells...
August 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26195790/the-xist-rna-prc2-complex-at-20-nm-resolution-reveals-a-low-xist-stoichiometry-and-suggests-a-hit-and-run-mechanism-in-mouse-cells
#20
Hongjae Sunwoo, John Y Wu, Jeannie T Lee
X-chromosome inactivation (XCI) is initiated by the long noncoding RNA Xist, which coats the inactive X (Xi) and targets Polycomb repressive complex 2 (PRC2) in cis. Epigenomic analyses have provided significant insight into Xist binding patterns and chromatin organization of the Xi. However, such epigenomic analyses are limited by averaging of population-wide dynamics and do not inform behavior of single cells. Here we view Xist RNA and the Xi at 20-nm resolution using STochastic Optical Reconstruction Microscopy (STORM) in mouse cells...
August 4, 2015: Proceedings of the National Academy of Sciences of the United States of America
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