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https://www.readbyqxmd.com/read/28167697/prc2-is-dispensable-for-hotair-mediated-transcriptional-repression
#1
Manuela Portoso, Roberta Ragazzini, Živa Brenčič, Arianna Moiani, Audrey Michaud, Ivaylo Vassilev, Michel Wassef, Nicolas Servant, Bruno Sargueil, Raphaël Margueron
Long non-coding RNAs (lncRNAs) play diverse roles in physiological and pathological processes. Several lncRNAs have been suggested to modulate gene expression by guiding chromatin-modifying complexes to specific sites in the genome. However, besides the example of Xist, clear-cut evidence demonstrating this novel mode of regulation remains sparse. Here, we focus on HOTAIR, a lncRNA that is overexpressed in several tumor types and previously proposed to play a key role in gene silencing through direct recruitment of Polycomb Repressive Complex 2 (PRC2) to defined genomic loci...
February 6, 2017: EMBO Journal
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
#2
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...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28134930/xist-dependent-imprinted-x-inactivation-and-the-early-developmental-consequences-of-its-failure
#3
Maud Borensztein, Laurène Syx, Katia Ancelin, Patricia Diabangouaya, Christel Picard, Tao Liu, Jun-Bin Liang, Ivaylo Vassilev, Rafael Galupa, Nicolas Servant, Emmanuel Barillot, Azim Surani, Chong-Jian Chen, Edith Heard
The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryos, we found that the initiation of imprinted X-chromosome inactivation absolutely requires Xist. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst and to failure to activate the extraembryonic pathway that is essential for postimplantation development...
January 30, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28133578/selection-and-evaluation-of-reference-genes-for-analysis-of-mouse-mus-musculus-sex-dimorphic-brain-development
#4
Tanya T Cheung, Mitchell K Weston, Megan J Wilson
The development of the brain is sex-dimorphic, and as a result so are many neurological disorders. One approach for studying sex-dimorphic brain development is to measure gene expression in biological samples using RT-qPCR. However, the accuracy and consistency of this technique relies on the reference gene(s) selected. We analyzed the expression of ten reference genes in male and female samples over three stages of brain development, using popular algorithms NormFinder, GeNorm and Bestkeeper. The top ranked reference genes at each time point were further used to quantify gene expression of three sex-dimorphic genes (Wnt10b, Xist and CYP7B1)...
2017: PeerJ
https://www.readbyqxmd.com/read/28132817/systematic-mapping-of-rna-chromatin-interactions-in%C3%A2-vivo
#5
Bharat Sridhar, Marcelo Rivas-Astroza, Tri C Nguyen, Weizhong Chen, Zhangming Yan, Xiaoyi Cao, Lucie Hebert, Sheng Zhong
RNA molecules can attach to chromatin. It remains difficult to know what RNAs are associated with chromatin and where the genomic target loci of these RNAs are. Here, we present MARGI (mapping RNA-genome interactions), a technology to massively reveal native RNA-chromatin interactions from unperturbed cells. The gist of this technology is to ligate chromatin-associated RNAs (caRNAs) with their target genomic sequences by proximity ligation, forming RNA-DNA chimeric sequences, which are converted to a sequencing library for paired-end sequencing...
January 25, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28125731/correlated-5-hydroxymethylcytosine-5hmc-and-gene-expression-profiles-underpin-gene-and-organ-specific-epigenetic-regulation-in-adult-mouse-brain-and-liver
#6
I-Hsuan Lin, Yi-Fan Chen, Ming-Ta Hsu
BACKGROUND: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology. METHODS: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing...
2017: PloS One
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
#7
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/28068310/visualizing-the-secondary-and-tertiary-architectural-domains-of-lncrna-repa
#8
Fei Liu, Srinivas Somarowthu, Anna Marie Pyle
Long noncoding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6-kb mouse lncRNA comprising the same sequence as the 5' region of Xist, including A and F repeats. It has been proposed to facilitate the initiation and spread of X-chromosome inactivation, although its exact role is poorly understood. To gain insight into the molecular mechanism of RepA and Xist, we determined a complete phylogenetically validated secondary-structural map of RepA through SHAPE and DMS chemical probing of a homogeneously folded RNA in vitro...
March 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28059474/csa-promotes-xist-expression-to-regulate-human-trophoblast-cells-proliferation-and-invasion-through-mir-144-titin-axis
#9
Nanhui Yu, Ying Liang, Hong Zhu, Hongying Mo, Haiping Pei
In our previous study, we revealed that Cyclosporin A (CsA) could inhibit miR-144 expression to regulate proliferation and invasion of human trophoblast (HT) cells through miR-144 targeting titin. This partially demonstrated the mechanism by which CsA promotes titin expression to increase the vitality of HT cells. However, the mechanism by which CsA inhibits miR-144 expression remains to be investigated. Recently, the interaction between lncRNA and miRNA has been frequently reported to play major role in several biological processes...
January 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28034840/establishment-of-porcine-xist-knockout-model-using-crispr-cas9-system
#10
Li Guoling, Zhong Cuili, Ni Sheng, Liu Dewu, Cai Gengyuan, Li Zicong, Yang Huaqiang, Wu Zhenfang
Somatic cell nuclear transfer technique has great applications in livestock breeding, production of genetically modified animals, rescue of endangered species and treatment of human diseases. However, the currently low efficiency in animals cloning, an average of less than 5%, greatly hindered the rapid development of this technique. Among many factors which affect the efficiency of cloning pigs, X chromosome inactivation is an important one. Moreover, Xist gene is closely related to X chromosome inactivation, suggesting that it may directly or indirectly affects cloning efficiency...
December 20, 2016: Yi Chuan, Hereditas
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/27989768/xact-noncoding-rna-competes-with-xist-in-the-control-of-x-chromosome-activity-during-human-early-development
#12
Céline Vallot, Catherine Patrat, Amanda J Collier, Christophe Huret, Miguel Casanova, Tharvesh M Liyakat Ali, Matteo Tosolini, Nelly Frydman, Edith Heard, Peter J Rugg-Gunn, Claire Rougeulle
Sex chromosome dosage compensation is essential in most metazoans, but the developmental timing and underlying mechanisms vary significantly, even among placental mammals. Here we identify human-specific mechanisms regulating X chromosome activity in early embryonic development. Single-cell RNA sequencing and imaging revealed co-activation and accumulation of the long noncoding RNAs (lncRNAs) XACT and XIST on active X chromosomes in both early human pre-implantation embryos and naive human embryonic stem cells...
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
#13
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/27934601/establishment-of-human-embryonic-stem-cell-line-with-a-complex-abnormal-karyotype-and-the-stable-xist-expression
#14
Leiyu Deng, Dehua Cheng, Guangxiu Lu, Ge Lin
The embryonic stem cell line chHES-3XISTa was derived from heterogeneous chHES-3 cells. chHES-3XISTa showed a new abnormal karyotype of 46,XX with 8 derivation chromosomes and expressed X inactive specific transcript (XIST) in continual culture. Tri-methylation of H3 Lys-27 (H3K27me3) punctate enrichment located in RNA Polymerase II hole was also found in all chHES-3XISTa cells. Pluripotent markers and differentiate capability in vitro were confirmed by immunochemistry staining.
November 5, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27911852/long-non-coding-rna-xist-promotes-cell-growth-and-invasion-through-regulating-mir-497-macc1-axis-in-gastric-cancer
#15
Lei Ma, Yongjian Zhou, Xiaojun Luo, Hai Gao, Xubin Deng, Yingjie Jiang
Abnormal expression of long non-coding RNA (lncRNAs) often contributes to unrestricted growth and invasion of cancer cells. LncRNA XIST expression is up-regulated in several cancers, however, its modulatory mechanism in gastric cancer (GC) has not been elucidated. In the present study, we found that XIST expression was significantly increased in GC tissues and cell lines. LncRNA XIST promoted cell cycle progression from the G1 phase to the S phase and protected cells from apoptosis, which contributed to GC cell growth...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27899965/increased-expression-of-long-non-coding-rna-xist-predicts-favorable-prognosis-of-cervical-squamous-cell-carcinoma-subsequent-to-definitive-chemoradiation-therapy
#16
Reiko Kobayashi, Ryu Miyagawa, Hideomi Yamashita, Teppei Morikawa, Kae Okuma, Masashi Fukayama, Kuni Ohtomo, Keiichi Nakagawa
The present retrospective study aimed to examine the association between the expression of long non-protein-coding RNAs (lncRNAs) and clinical prognosis in the pretreatment formalin-fixed, paraffin-embedded (FFPE) tissue samples of cervical squamous cell carcinoma patients that underwent platinum-based chemoradiation therapy. Between 2001 and 2013, 49 consecutive patients with squamous cell cervical carcinoma were selected for the present study (median follow-up period, 44.1 months). The patients possessed an International Federation of Gynecology and Obstetrics stage of IB1/IIA1 (with pelvic lymph node metastasis), IB2 or IIA2-IVA, and had been treated with definitive chemoradiation therapy...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899588/a-high-throughput-approach-to-profile-rna-structure
#17
Riccardo Delli Ponti, Stefanie Marti, Alexandros Armaos, Gian Gaetano Tartaglia
Here we introduce the Computational Recognition of Secondary Structure (CROSS) method to calculate the structural profile of an RNA sequence (single- or double-stranded state) at single-nucleotide resolution and without sequence length restrictions. We trained CROSS using data from high-throughput experiments such as Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE; Mouse and HIV transcriptomes) and Parallel Analysis of RNA Structure (PARS; Human and Yeast transcriptomes) as well as high-quality NMR/X-ray structures (PDB database)...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27880931/an-xist-related-small-rna-regulates-kras-g-quadruplex-formation-beyond-x-inactivation
#18
Yuli C Chang, Chien-Chih Chiu, Chung-Yee Yuo, Wen-Ling Chan, Ya-Sian Chang, Wen-Hsin Chang, Shou-Mei Wu, Han-Lin Chou, Ta-Chih Liu, Chi-Yu Lu, Wen-Kuang Yang, Jan-Gowth Chang
X-inactive-specific transcript (XIST), a long non-coding RNA, is essential for the initiation of X-chromosome inactivation. However, little is known about other roles of XIST in the physiological process in eukaryotic cells. In this study, the bioinformatics approaches revealed XIST could be processed into a small non-coding RNA XPi2. The XPi2 RNA was confirmed by a northern blot assay; its expression was gender-independent, suggesting the role of XPi2 was beyond X-chromosome inactivation. The pull-down assay combined with LC-MS-MS identified two XPi2-associated proteins, nucleolin and hnRNP A1, connected to the formation of G-quadruplex...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27870435/a-general-theory-of-sexual-differentiation
#19
REVIEW
Arthur P Arnold
A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequality leads to male-specific effects of the Y chromosome, including expression of the testis-determining gene Sry that causes differentiation of testes. Thus, Sry sets up lifelong sex differences in effects of gonadal hormones. Y genes also act outside of the gonads to cause male-specific effects...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27819659/a-statistical-test-for-conserved-rna-structure-shows-lack-of-evidence-for-structure-in-lncrnas
#20
Elena Rivas, Jody Clements, Sean R Eddy
Many functional RNAs have an evolutionarily conserved secondary structure. Conservation of RNA base pairing induces pairwise covariations in sequence alignments. We developed a computational method, R-scape (RNA Structural Covariation Above Phylogenetic Expectation), that quantitatively tests whether covariation analysis supports the presence of a conserved RNA secondary structure. R-scape analysis finds no statistically significant support for proposed secondary structures of the long noncoding RNAs HOTAIR, SRA, and Xist...
January 2017: Nature Methods
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