XIST derepression in active X chromosome hinders pig somatic cell nuclear transfer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA419728 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6321510_1.fastq.gz | Fastqsanger.gz | |||
| SRR6321510_2.fastq.gz | Fastqsanger.gz | |||
| SRR6321520_1.fastq.gz | Fastqsanger.gz | |||
| SRR6321520_2.fastq.gz | Fastqsanger.gz | |||
| SRR6321511_1.fastq.gz | Fastqsanger.gz |
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Project description:Pig cloning by somatic cell nuclear transfer (SCNT) remains extremely inefficient and many cloned embryos undergo abnormal development. Here by profiling transcriptome expression, we observed dysregulated chromosome-wide gene expression in every chromosome and identified a considerable number of genes that are aberrantly expressed in the abnormal cloned embryos. In particular, XIST, a long noncoding RNA gene, showed highly ectopic expression in abnormal embryos. We also proved that nullification of the XIST gene in donor cells can correct aberrant gene expression in cloned embryos and enhance long term development capacity of the embryos. Furthermore, the increased quality of XIST-deficient embryos was associated with the global H3K9me3 reduction. Injection of H3K9me demethylase Kdm4A into NT embryos could improve the development of preimplantation stage embryos. However, Kdm4A addition also induced XIST derepression in the active X chromosome, thus was not able to enhance the in vivo long term developmental capacity of porcine NT embryos.
2018-01-01 | GSE107302 | GEO
Project description:Pig cloning by somatic cell nuclear transfer (SCNT) remains extremely inefficient, and many cloned embryos undergo abnormal development. Here, by profiling transcriptome expression, we observed dysregulated chromosome-wide gene expression in every chromosome and identified a considerable number of genes that are aberrantly expressed in the abnormal cloned embryos. In particular, XIST, a long non-coding RNA gene, showed high ectopic expression in abnormal embryos. We also proved that nullification of the XIST gene in donor cells can normalize aberrant gene expression in cloned embryos and enhance long-term development capacity of the embryos. Furthermore, the increased quality of XIST-deficient embryos was associated with the global H3K9me3 reduction. Injection of H3K9me demethylase Kdm4A into NT embryos could improve the development of pre-implantation stage embryos. However, Kdm4A addition also induced XIST derepression in the active X chromosome and thus was not able to enhance the in vivo long-term developmental capacity of porcine NT embryos.
| S-EPMC5830944 | biostudies-literature
Project description:Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient because of aberrant genomic reprogramming. In addition to random reprogramming errors, we hypothesized the presence of specific errors as evidenced by common anomalies among clones. We found that Xist, which normally inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa normalized global gene expression and produced about a 10-fold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically downregulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning, which provide promising targets for breakthroughs in SCNT cloning technology. Gene expression were measured in mouse in vitro fertilized and somatic cell cloned blastocysts. More than three biological replicates were performed in each group using defferent nuclear donor cells.
2010-09-16 | E-GEOD-23181 | biostudies-arrayexpress
Project description:Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient because of aberrant genomic reprogramming. In addition to random reprogramming errors, we hypothesized the presence of specific errors as evidenced by common anomalies among clones. We found that Xist, which normally inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa normalized global gene expression and produced about a 10-fold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically downregulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning, which provide promising targets for breakthroughs in SCNT cloning technology.
2010-09-16 | GSE23181 | GEO
Project description:Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. Here we investigate the localization mechanisms of Xist during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X-chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X-chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X-chromosome. Xist initially accumulates on the periphery of actively transcribed regions and requires its silencing domain to spread across active regions. This suggests a model where Xist coats the entire X-chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations. We examined the genomic localization of the Xist lncRNA using RNA Antisense Purification (RAP) in multiple cell contexts: 1) differentiated female cells (MLFs); 2) a time-course of Xist localization in male embryonic stem (ES) cells where the endogenous Xist promoter is replaced by a tet-inducible one (pSM33); 3) a time-course of Xist localization in differentiating female ES cells (F1 2-1); and 4) wild-type (delXF6) and A-repeat deletion (delSXC9) Xist transgenes incorporated into the Hprt locus under the control of a tet-inducible promoter.
2013-05-30 | E-GEOD-46918 | biostudies-arrayexpress
Project description:Xist orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the 3-dimensional structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here we show that Xist directly interacts with the Lamin B Receptor (LBR), an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing. We show that this interaction recruits the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the accessibility of DNA thereby enabling Xist, and its silencing proteins, to spread across the X to silence transcription. We examined the genomic localization of the Xist lncRNA using RNA Antisense Purification (RAP) in male mouse ES cells where the endogenous Xist promoter is replaced by a tet-inducible one (pSM33) containing 1) wild-type Xist (WT), 2) A-repeat deletion Xist (dA), 3) LBR binding site deletion Xist (dLBS), 4) dLBS-Xist rescued with LMNB1 (LMNB1Res), 5) LBR CRISPRi knock down (LBRKD), or 6) SHARP CRISPRi knock down (SHARPKD).
2016-07-24 | E-GEOD-80510 | biostudies-arrayexpress
Project description:Xist-mediated Chromosome Inactivation
| PRJNA489702 | ENA
Project description:The role of Xist-mediated Polycomb recruitment in the initiation of X-chromosome inactivation
2019-08-29 | PXD014287 | Pride
Project description:Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. Here we investigate the localization mechanisms of Xist during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X-chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X-chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X-chromosome. Xist initially accumulates on the periphery of actively transcribed regions and requires its silencing domain to spread across active regions. This suggests a model where Xist coats the entire X-chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.
2013-05-30 | GSE46918 | GEO
Project description:Purpose: Compare the transcriptome of homogeneous XIST+ and XIST- hES cell populations. Methods: We isolated homogeneous XIST+ and XIST- cell populations. The XIST+ cells correspond to cells with a XIST cloud and one ATRX pinpoint. The XIST- cells correspond to cells with no XIST cloud and one ATRX pinpoint. Results: We took advantage of the clonal pattern of X-chromosome inactivation in H9 cells and analyzed the data in an allelic manner. By comparing the RNA-Seq data with known H9 SNPs, we identified genomic positions which were relaxed from XCI in XIST- cells compared to XIST+ cells. Conclusions: Genic as well as unannotated transcripts are massively relaxed from XCI in H9 cells when XIST expression is lost, however, this reactivation is only partial and a large region around the centromere is protected from relaxation of silencing. Total RNA (rRNA depleted) profiles of XIST+ and XIST- human embryonic stem cells
2012-12-21 | E-GEOD-39757 | biostudies-arrayexpress