Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (Infinium HumanMethylation450 Beadchip)

ABSTRACT: Differentiation is accompanied by extensive epigenomic reprogramming, leading to the repression of stemness factors and the transcriptional maintenance of activated lineage-specific genes. Here we used the mammalian Hoxa cluster of developmental genes as a model system to follow changes in DNA modification patterns during retinoic acid induced differentiation. We found the inactive cluster to be marked by defined patterns of 5-methylcytosine (5mC). Upon the induction of differentiation, the active anterior part of the cluster became increasingly enriched in 5-hydroxymethylcytosine (5hmC), following closely the colinear activation pattern of the gene array, which was paralleled by the reduction of 5mC. Depletion of the 5hmC generating dioxygenase Tet2 impaired the maintenance of Hoxa activity and partially restored 5mC levels. Our results indicate that gene specific 5mC-5hmC conversion by Tet2 is crucial for the maintenance of active chromatin states at lineage-specific loci.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32362 | GEO | 2012/05/03

SECONDARY ACCESSION(S): PRJNA155509

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (Infinium HumanMethylation450 Beadchip)

Project description:Differentiation is accompanied by extensive epigenomic reprogramming, leading to the repression of stemness factors and the transcriptional maintenance of activated lineage-specific genes. Here we used the mammalian Hoxa cluster of developmental genes as a model system to follow changes in DNA modification patterns during retinoic acid induced differentiation. We found the inactive cluster to be marked by defined patterns of 5-methylcytosine (5mC). Upon the induction of differentiation, the active anterior part of the cluster became increasingly enriched in 5-hydroxymethylcytosine (5hmC), following closely the colinear activation pattern of the gene array, which was paralleled by the reduction of 5mC. Depletion of the 5hmC generating dioxygenase Tet2 impaired the maintenance of Hoxa activity and partially restored 5mC levels. Our results indicate that gene specific 5mC-5hmC conversion by Tet2 is crucial for the maintenance of active chromatin states at lineage-specific loci. Genome wide DNA methylation profiling of uninduced and retinoic acid (RA) induced NTera2/D1 embryocarcinoma cells (NT2). Bisulphite converted DNA of uninduced, 7d RA and 14d RA treated NT2 cells were hybridised to the Illumina Infinium HumanMethylation450 Beadchip.

2012-05-02 | E-GEOD-32362 | biostudies-arrayexpress

Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (MeDIP-Seq)

Project description:Differentiation is accompanied by extensive epigenomic reprogramming, leading to the repression of stemness factors and the transcriptional maintenance of activated lineage-specific genes. Here we used the mammalian Hoxa cluster of developmental genes as a model system to follow changes in DNA modification patterns during retinoic acid induced differentiation. We found the inactive cluster to be marked by defined patterns of 5-methylcytosine (5mC). Upon the induction of differentiation, the active anterior part of the cluster became increasingly enriched in 5-hydroxymethylcytosine (5hmC), following closely the colinear activation pattern of the gene array, which was paralleled by the reduction of 5mC. Depletion of the 5hmC generating dioxygenase Tet2 impaired the maintenance of Hoxa activity and partially restored 5mC levels. Our results indicate that gene specific 5mC-5hmC conversion by Tet2 is crucial for the maintenance of active chromatin states at lineage-specific loci. Examination of 5-methylcytosine (MeDIP-seq) and 5-hydroxymethylcytosine (hMeDIP-seq) at the HOXA cluster in 2 different developmental stages of a pluripotent cancer cell line.

2012-05-02 | E-GEOD-33129 | biostudies-arrayexpress

Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (MeDIP-Seq)

2012-05-03 | GSE33129 | GEO

Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster

Project description:This SuperSeries is composed of the following subset Series: GSE32362: Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (Illumina HumanMethylation450 BeadChip) GSE33129: Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster (Illumina HiSeq2000 sequencing) Refer to individual Series

2012-05-02 | E-GEOD-33130 | biostudies-arrayexpress

Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency

Project description:Cytosine DNA bases can be methylated by DNA methyltransferases and subsequently oxidized by TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are considered demethylation intermediates as well as stable epigenetic marks. To dissect the contribution of these cytosine modifying enzymes, we generated combinations of Tet knockout (KO) embryonic stem cells (ESCs) and systematically measured protein and DNA modification levels at the transition from naive to primed pluripotency. Whereas the increase of genomic 5-methylcytosine (5mC) levels during exit from pluripotency correlated with an upregulation of the de novo DNA methyltransferases DNMT3A and DNMT3B, the subsequent oxidation steps turned out to be far more complex. The strong increase of oxidized cytosine bases (5hmC, 5fC, and 5caC) was accompanied by a drop in TET2 levels, yet the analysis of KO cells suggested that TET2 is responsible for most 5fC formation. The comparison of modified cytosine and enzyme levels in Tet KO cells revealed distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation arguing against a processive mechanism of 5mC oxidation. The apparent independent steps of 5hmC and 5fC formation suggest yet to be identified mechanisms regulating TET activity and may constitute another layer of epigenetic regulation.

2020-07-24 | PXD019514 | Pride

Combined deficiency of Tet1 and Tet2 is compatible with development but leads to epigenetic instability

Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 and Tet2 mediate 5hmC generation in mouse embryonic stem cells (ESCs) and various embryonic and adult tissues. To investigate the effects of combined deficiency of Tet1 and Tet2 on pluripotency and development, we have generated Tet1 and Tet2 double knockout (DKO) ESCs and mice. DKO ESCs were depleted of 5hmC, but remained pluripotent with subtle defects in differentiation and changes in gene expression. Double mutant embryos and chimeras exhibited mid-gestation defects and postnatal DKO mice displayed partially penetrant neonatal lethality and stochastic perturbation of imprinting. Viable DKO animals developed normally to adulthood but had reduced 5hmC level, increased 5mC level and lacked 5hmC in germ cells. Nevertheless, DKO mice of both sexes were fertile with females having smaller ovaries and reduced fertility. Our data suggest that both Tet1 and Tet2 contribute to 5hmC levels during development. Their combined loss does not block differentiation and embryogenesis, but leads to partially penetrant embryonic and perinatal abnormalities and compromised viability. Moreover, the presence of substantial levels of 5hmC in DKO embryos and adult mice suggests a significant contribution of Tet3 in hydroxylation of 5mC during development. Methylation patterns in tissue samples from a series of wt and Tet1/Tet2 DKO embryos, neonates and adults were generated using methylated DNA immunoprecipitation with antibodies against 5mC (MeDIP) and 5hmC (hMeDIP) followed by deep sequencing.

2013-02-01 | E-GEOD-42396 | biostudies-arrayexpress

Control of 5mC and 5hmC by TET dioxygenases in human embryonic carcinoma cells [MBD-Seq]

Project description:The TET family of dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), but their involvement in establishing normal 5mC patterns during mammalian development and their contributions to aberrant control of 5mC during cellular transformation remains largely unknown. We depleted TET1, TET2, and TET3 by siRNA in a pluripotent embryonic carcinoma cell model and examined the impact on genome-wide 5mC and 5hmC patterns. TET1 depletion yielded widespread reduction of 5hmC, while depletion of TET2 and TET3 reduced 5hmC at a subset of TET1 targets suggesting functional co-dependence. TET2 or TET3-depletion also caused increased 5hmC, suggesting they play a major role in 5hmC removal. All TETs prevent hypermethylation throughout the genome, a finding dramatically illustrated in CpG island shores, where TET depletion resulted in prolific hypermethylation. Surprisingly, TETs also promote methylation, as hypomethylation was associated with 5hmC reduction. TET function was highly specific to chromatin environment: 5hmC maintenance by all TETs occurred at polycomb-marked chromatin and genes expressed at moderate levels; 5hmC removal by TET2 is associated with highly transcribed genes enriched for H3K4me3 and H3K36me3. Importantly, genes prone to hypermethylation in cancer become depleted of 5hmC with TET deficiency, suggesting the TETs normally promote 5hmC at these loci, and all three TETs are required for 5hmC enrichment at enhancers, a condition necessary for expression of adjacent genes. These results provide novel insight into the division of labor among TET proteins and reveal an important connection of TET activity with chromatin landscape and gene expression. Methylation and hydroxymethylation profiling by affinity-based high throughput sequencing

2014-06-14 | E-GEOD-51902 | biostudies-arrayexpress

Control of 5mC and 5hmC by TET dioxygenases in human embryonic carcinoma cells [Microarray]

Project description:The TET family of dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), but their involvement in establishing normal 5mC patterns during mammalian development and their contributions to aberrant control of 5mC during cellular transformation remains largely unknown. We depleted TET1, TET2, and TET3 by siRNA in a pluripotent embryonic carcinoma cell model and examined the impact on genome-wide 5mC and 5hmC patterns. TET1 depletion yielded widespread reduction of 5hmC, while depletion of TET2 and TET3 reduced 5hmC at a subset of TET1 targets suggesting functional co-dependence. TET2 or TET3-depletion also caused increased 5hmC, suggesting they play a major role in 5hmC removal. All TETs prevent hypermethylation throughout the genome, a finding dramatically illustrated in CpG island shores, where TET depletion resulted in prolific hypermethylation. Surprisingly, TETs also promote methylation, as hypomethylation was associated with 5hmC reduction. TET function was highly specific to chromatin environment: 5hmC maintenance by all TETs occurred at polycomb-marked chromatin and genes expressed at moderate levels; 5hmC removal by TET2 is associated with highly transcribed genes enriched for H3K4me3 and H3K36me3. Importantly, genes prone to hypermethylation in cancer become depleted of 5hmC with TET deficiency, suggesting the TETs normally promote 5hmC at these loci, and all three TETs are required for 5hmC enrichment at enhancers, a condition necessary for expression of adjacent genes. These results provide novel insight into the division of labor among TET proteins and reveal an important connection of TET activity with chromatin landscape and gene expression. Affymetrix gene expression Human ST1.0 microarray of NCCIT human embryonic carcinoma cells (4 samples in duplicate).

2014-06-14 | E-GEOD-51901 | biostudies-arrayexpress

Combined deficiency of Tet1 and Tet2 is compatible with development but leads to epigenetic instability

2013-02-01 | GSE42396 | GEO

Combined loss of Tet1 and Tet2 promotes B-cell, but not myeloid malignancies in mice

Project description:TET1/2/3 are methylcytosine dioxygenases regulating cytosine hydroxymethylation in the genome. Tet1 and Tet2 are abundantly expressed in HSC/HPCs and implicated in the pathogenesis of hematological malignancies. Tet2-deletion in mice causes myeloid malignancies, while Tet1-null mice develop B-cell lymphoma after an extended period of latency. Interestingly, TET1 and TET2 were often concomitantly down-regulated in acute B-lymphocytic leukemia. Here, we investigated the overlapping and non-redundant functions of Tet1/Tet2 in HSC maintenance and development of hematological malignancies using Tet1/2 double knockout (DKO) mice. DKO and Tet2-/- HSC/HPCs had overlapping and unique 5hmC and 5mC profiles and behaved differently. DKO mice exhibited strikingly decreased incidence and delayed onset of myeloid malignancies compared to Tet2-/- mice and in contrast developed lethal B-cell malignancies. Transcriptome analysis of DKO tumors revealed expression changes in many genes dysregulated in human B-cell malignancies, such as LMO2, BCL6 and MYC. These results highlight the critical roles of TET1 or TET2 individually and their cross-talks in the pathogenesis of hematological malignancies. Given the role of Tet proteins in 5mC oxidation, we employed a previously established chemical labeling and affinity purification method coupled with high-throughput sequencing (hMe-Seal) to profile the genome-wide distribution of 5hmC, as well as methylated DNA immunoprecipitation (MeDIP) coupled with high-throughput sequencing (MeDIP-seq) to profile 5mC using BM LK cells purified from young WT, Tet2-/- and DKO mice (6-10 wks old).

2015-11-12 | E-GEOD-73611 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data