Rinf regulates pluripotency network and Tet enzymes in embryonic stem cells (ESCs)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA545693 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9165580.fastq.gz | Fastqsanger.gz | |||
| SRR9165590.fastq.gz | Fastqsanger.gz | |||
| SRR9165581.fastq.gz | Fastqsanger.gz | |||
| SRR9165591.fastq.gz | Fastqsanger.gz | |||
| SRR9165582.fastq.gz | Fastqsanger.gz |
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Project description:In this study: (1) We have mapped the genome wide binding distribution and enrichment of Rinf/CXXC5 at genes and regulatory regions in mouse ESCs by ChIP-seq using a specific antibody against Rinf. (2) We have examined the role of Rinf in regulation of ESC gene expression programs by performing transcriptomic analysis of Rinf wild type and knockout ESCs by RNA-seq to identify differentially expressed genes. (3) We have investigated the role of Rinf in differentiation and lineage specification programs of ESCs by analyzing the transcriptomic profile of wild type and Rinf–/– ESCs during differentiation to embroyoid bodies (EBs) at three time points (day 0, 3, 6).
2019-08-05 | GSE132025 | GEO
Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) and are dynamically expressed in various embryonic and adult cell types. While loss of individual Tet enzymes or combined deficiency of Tet1/2 allows for embryogenesis, the effect of complete loss of Tet activity and 5hmC marks in development is not established. We have generated Tet1/2/3 triple knockout (TKO) mouse embryonic stem cells (ESCs) and examined their developmental potential. Combined deficiency of all three Tets depleted 5hmC and impaired ESC differentiation as seen in poorly differentiated TKO embryoid bodies (EBs) and teratomas. Consistent with impaired differentiation, TKO-ESCs contributed poorly to chimeric embryos and could not support embryonic development. Global gene expression and methylome analyses of TKO-EBs revealed promoter hypermethylation and deregulation of genes implicated in embryonic development and differentiation. These findings suggest a requirement for Tet- and 5hmC-mediated DNA demethylation in proper regulation of gene expression during differentiation of ESCs and development. To quantify global gene expression in differentiating embryoid bodies (EBs) derived from wild type (WT) and Tet triple knockout (TKO), TKO and WT mouse embryonic stem cells (ESCs) were differentiated in vitro to EBs and cultured for 10 days. RNA was extracted using Qiagen RNeasy kit and subjected to microarray analysis. Global gene expression profile of two technical replicas of WT embryoid bodies (2 samples in total) was compared to two technical replicas of two independent TKO embryoid bodies (4 TKO samples in total).
2014-04-14 | E-GEOD-55574 | biostudies-arrayexpress
Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) and are dynamically expressed in various embryonic and adult cell types. While loss of individual Tet enzymes or combined deficiency of Tet1/2 allows for embryogenesis, the effect of complete loss of Tet activity and 5hmC marks in development is not established. We have generated Tet1/2/3 triple knockout (TKO) mouse embryonic stem cells (ESCs) and examined their developmental potential. Combined deficiency of all three Tets depleted 5hmC and impaired ESC differentiation as seen in poorly differentiated TKO embryoid bodies (EBs) and teratomas. Consistent with impaired differentiation, TKO-ESCs contributed poorly to chimeric embryos and could not support embryonic development. Global gene expression and methylome analyses of TKO-EBs revealed promoter hypermethylation and deregulation of genes implicated in embryonic development and differentiation. These findings suggest a requirement for Tet- and 5hmC-mediated DNA demethylation in proper regulation of gene expression during differentiation of ESCs and development.
2014-04-14 | GSE55574 | GEO
Project description:Tet enzymes (Tet1/2/3) catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) and are dynamically expressed in various embryonic and adult cell types. While loss of individual Tet enzymes or combined deficiency of Tet1/2 allows for embryogenesis, the effect of complete loss of Tet activity and 5hmC marks in development has not been established. To define the role of Tet enzymes and 5hmC in development we have generated Tet1, Tet2 and Tet3 triple knockout (TKO) mouse embryonic stem cells (ESCs) and examined their developmental potential in vitro and in vivo. Combined deficiency of all three Tet enzymes led to complete depletion of 5hmC and impaired ESC differentiation as seen in poorly differentiated TKO embryoid bodies and teratomas. Consistent with impaired differentiation, TKO ES cells exhibited limited contribution to the chimeric embryos and could not support embryonic development in tetraploid complementation assays. Gene expression profiles and genome wide methylome analyses of TKO embryoid bodies revealed promoter hypermethylation and deregulation of genes implicated in embryonic development and differentiation. These findings suggest a requirement for Tet and 5hmC-mediated DNA demethylation in proper regulation of gene expression during differentiation of embryonic stem cells and development. Methylation patterns in tissue samples from a series of wt and Tet1/Tet2 DKO embryos, neonates and adults were generated using ethylated DNA immunoprecipitation with antibodies against 5mC (MeDIP) and 5hmC (hMeDIP) followed by deep sequencing.
2014-04-17 | E-GEOD-55049 | biostudies-arrayexpress
Project description:Tet enzymes (Tet1/2/3) catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) and are dynamically expressed in various embryonic and adult cell types. While loss of individual Tet enzymes or combined deficiency of Tet1/2 allows for embryogenesis, the effect of complete loss of Tet activity and 5hmC marks in development has not been established. To define the role of Tet enzymes and 5hmC in development we have generated Tet1, Tet2 and Tet3 triple knockout (TKO) mouse embryonic stem cells (ESCs) and examined their developmental potential in vitro and in vivo. Combined deficiency of all three Tet enzymes led to complete depletion of 5hmC and impaired ESC differentiation as seen in poorly differentiated TKO embryoid bodies and teratomas. Consistent with impaired differentiation, TKO ES cells exhibited limited contribution to the chimeric embryos and could not support embryonic development in tetraploid complementation assays. Gene expression profiles and genome wide methylome analyses of TKO embryoid bodies revealed promoter hypermethylation and deregulation of genes implicated in embryonic development and differentiation. These findings suggest a requirement for Tet and 5hmC-mediated DNA demethylation in proper regulation of gene expression during differentiation of embryonic stem cells and development.
2014-04-17 | GSE55049 | GEO
Project description:Mammalian embryo development begins in transcriptional silence followed by activation of thousands of genes. Reprogramming of DNA methylation is integral to embryogenesis and linked to Tet enzymes; however, their function in early development is not fully understood. Here, we generated combined deficiencies of all three Tet enzymes in mouse oocytes and observed arrest at 2-cell stage with the most severe phenotype linked to Tet2. Gene expression analysis revealed that Tet enzymes are required for completion of embryonic genome activation. Our results demonstrate that Tet enzymes have non-redundant roles and are key components of EGA in mammalian embryos.
2021-11-22 | GSE57063 | GEO
Project description:In this study we have examined the role of Tet enzymes in regulation of embryonic Endothelial cells (ECs) and Hematopoietic stem and progenitor cells (HSPCs). We have performed transcriptomic and methylation analyses of Tet deficient and wild type ECs and HSPCs isolated from E11.5 embryonic aorta-gonad-mesonephros (AGM) to identify differentially expressed genes and differentially methylated regions.
2022-02-19 | GSE176391 | GEO
Project description:How embryonic stem cells (ESC) commit to specific cell lineages and ultimately yield all cell types of a fully formed organism remains a major question. ESC differentiation is accompanied by large-scale histone and DNA modifications, but the relations between these two categories of epigenetic changes are not understood. Here we demonstrate the hierarchical interplay between the histone deacetylase, sirtuin 6 (Sirt6), which targets acetylated histone H3 at lysines 9 and 56 (H3K9ac and H3K56ac), and the Tet (Ten-eleven translocation) enzymes, which convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). ESCs derived from Sirt6 knocSirt6 KOut (S6Sirt6 KO) mice are skewed towards neuroectoderm development. This phenotype is associated with derepression of Oct4, Sox2 and Nanog, which in turn causes an upregulation of Tet enzymes and elevated production of 5hmC. Genome-wide analysis revealed an upregulation of neuroectoderm genes marked with 5hmC in S6Sirt6 KO ESCs, thereby implicating Tet enzymes in the neuroectoderm-skewed differentiation phenotype of S6Sirt6 KO ESCs, which is fully rescued upon knockdown of Tets. We demonstrate a new role for Sirt6 as a chromatin regulator safeguarding the balance between pluripotency and differentiation through Tet-dependent regulation of 5hmC levels.
2015-03-12 | GSE65836 | GEO
Project description:Tet enzymes are required for mammalian embryonic hematopoiesis
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Project description:Dormancy is an essential biological process for the propagation of many life forms through generations and stressful conditions. Early embryos of many mammals are preservable for weeks to months within the uterus under dormancy, which can be induced in vitro through mTOR inhibition. Dormancy features silencing of the genome and abundant heterochromatin formation, which conflicts with the permissive and uncommitted genomic profile of pluripotent cells. Cellular strategies to maintain pluripotency in the fate of this conflict are not known. Here we probed chromatin regulation during embryonic stem cells’ (ESC) entry into dormancy to identify mechanisms that ensure faithful propagation of cellular identity through dormancy. We show a global increase in DNA methylation and loss of chromatin accessibility in dormant ESCs and find that TET DNA demethylases are essential to counteract this trend at key pluripotency regulatory elements, particularly at young LINE1 repeats and active enhancers. Demethylation of these targets by TETs is essential for transcription factor (TF) recruitment and transient chromatin decondensation before hypercompaction. We propose that key regulatory elements are bookmarked coordinately by TETs and TFs in dormancy for maintenance of cellular identity. Perturbation of TET activity compromises embryo survival through dormancy; whereas its enhancement improves survival rates. Our results reveal the first essential chromatin regulator in establishing mammalian embryonic dormancy and pave the way to building its temporal regulatory code in embryonic and adult tissues.
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