Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

5-Hydroxymethylcytosine: generation, fate, and genomic distribution.

ABSTRACT: 5-Methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) in mammalian cells by the ten-eleven translocation (Tet) family of dioxygenases. While 5mC has been extensively studied, we have just started to understand the distribution and function of 5hmC in mammalian genomes. Despite the fact that this new epigenetic mark has only been discovered three years ago, exciting progress has been made in understanding its generation, fate, and genomic distribution. In this review we discuss these progresses as well as the recent advance in the single-base resolution mapping of 5hmC.

SUBMITTER: Shen L

PROVIDER: S-EPMC4060438 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

5-Hydroxymethylcytosine: generation, fate, and genomic distribution.

Shen Li L Zhang Yi Y

Current opinion in cell biology 20130313 3

5-Methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) in mammalian cells by the ten-eleven translocation (Tet) family of dioxygenases. While 5mC has been extensively studied, we have just started to understand the distribution and function of 5hmC in mammalian genomes. Despite the fact that this new epigenetic mark has only been discovered three years ago, exciting progress has been made in understanding its generation, fate, and genomic distribution. In this review we discus ...[more]

PMID: 23498661

Similar Datasets

Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development.

Project description:Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered. Here we examine 5-hmC distribution during mammalian development and in cellular systems, and show that the developmental dynamics of 5-hmC are different from those of 5-methylcytosine (5-mC); in particular 5-hmC is enriched in embryonic contexts compared to adult tissues. A detectable 5-hmC signal appears in pre-implantation development starting at the zygote stage, where the paternal genome is subjected to a genome-wide hydroxylation of 5-mC, which precisely coincides with the loss of the 5-mC signal in the paternal pronucleus. Levels of 5-hmC are high in cells of the inner cell mass in blastocysts, and the modification colocalises with nestin-expressing cell populations in mouse post-implantation embryos. Compared to other adult mammalian organs, 5-hmC is strongly enriched in bone marrow and brain, wherein high 5-hmC content is a feature of both neuronal progenitors and post-mitotic neurons. We show that high levels of 5-hmC are not only present in mouse and human embryonic stem cells (ESCs) and lost during differentiation, as has been reported previously, but also reappear during the generation of induced pluripotent stem cells; thus 5-hmC enrichment correlates with a pluripotent cell state. Our findings suggest that apart from the cells of neuronal lineages, high levels of genomic 5-hmC are an epigenetic feature of embryonic cell populations and cellular pluri- and multi-lineage potency. To our knowledge, 5-hmC represents the first epigenetic modification of DNA discovered whose enrichment is so cell-type specific.

| S-EPMC3193467 | biostudies-literature

Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions.

Project description:Dynamically polarized membrane proteins define different cell boundaries and have an important role in intercellular communication-a vital feature of multicellular development. Efflux carriers for the signalling molecule auxin from the PIN family are landmarks of cell polarity in plants and have a crucial involvement in auxin distribution-dependent development including embryo patterning, organogenesis and tropisms. Polar PIN localization determines the direction of intercellular auxin flow, yet the mechanisms generating PIN polarity remain unclear. Here we identify an endocytosis-dependent mechanism of PIN polarity generation and analyse its developmental implications. Real-time PIN tracking showed that after synthesis, PINs are initially delivered to the plasma membrane in a non-polar manner and their polarity is established by subsequent endocytic recycling. Interference with PIN endocytosis either by auxin or by manipulation of the Arabidopsis Rab5 GTPase pathway prevents PIN polarization. Failure of PIN polarization transiently alters asymmetric auxin distribution during embryogenesis and increases the local auxin response in apical embryo regions. This results in ectopic expression of auxin pathway-associated root-forming master regulators in embryonic leaves and promotes homeotic transformation of leaves to roots. Our results indicate a two-step mechanism for the generation of PIN polar localization and the essential role of endocytosis in this process. It also highlights the link between endocytosis-dependent polarity of individual cells and auxin distribution-dependent cell fate establishment for multicellular patterning.

| S-EPMC2692841 | biostudies-literature

Genomic distribution of 5-hydroxymethylcytosine in mouse kidney and its relationship with gene expression

Project description:Ten-Elven Translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytonsie (5hmC). Our recent work found a decline in global 5hmC level in mouse kidney insulted by ischemia reperfusion (IR). However, the genomic distribution of 5hmC in mouse kidney and its relationship with gene expression remain elusive. Here, we profiled the DNA hydroxymethylome of mouse kidney by hMeDIP-seq and revealed that 5hmC is enriched in genic regions but depleted from intergenic regions. Correlation analyses showed that 5hmC enrichment in gene body is positively associated with gene expression level in mouse kidney. Moreover, IR injury-associated genes (both up- and down-regulated genes during renal IR injury) in mouse kidney exhibit significantly higher 5hmC enrichment in their gene body regions when compared to those un-changed genes. Collectively, our study not only provides the first DNA hydroxmethylome of kidney tissues but also suggests that DNA hyper-hydroxymethylation in gene body may be a novel epigenetic mark of IR injury-associated genes.

2016-04-01 | GSE79093 | GEO

Genomic distribution of 5-hydroxymethylcytosine in mouse kidney and its relationship with gene expression

2016-04-01 | E-GEOD-79093 | biostudies-arrayexpress

Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA.

Project description:The recent discovery of genomic 5-hydroxymethylcytosine (hmC) and mutations affecting the respective Tet hydroxylases in leukemia raises fundamental questions about this epigenetic modification. We present a sensitive method for fast quantification of genomic hmC based on specific transfer of radiolabeled glucose to hmC by a purified glucosyltransferase. We determined hmC levels in various adult tissues and differentiating embryonic stem cells and show a correlation with differential expression of tet genes.

| S-EPMC2965258 | biostudies-literature

Genomic mapping of 5-hydroxymethylcytosine in the human brain.

Project description:Methylation at the 5-position of cytosine is a well-studied epigenetic pathway. In addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) also referred to as the sixth DNA base have been detected in certain tissues, most notably the brain. However, the genomic distribution of this cytosine modification is unknown. Here, we have used an immunoprecipitation technique (5hmC-IP) to examine the occurrence of 5hmC in DNA from human brain frontal lobe tissue. The distribution of 5hmC was compared to that of 5mC. We show that 5hmC is more selectively targeted to genes than is 5mC. 5hmC is particularly enriched at promoters and in intragenic regions (gene bodies) but is largely absent from non-gene regions. 5hmC peaks at transcription start sites did not correlate with gene expression levels for promoters with intermediate or high CpG content. However, the presence of 5hmC in gene bodies was more positively correlated with gene expression levels than was the presence of 5mC. Promoters of testis-specific genes showed strong 5mC peaks in brain DNA but were almost completely devoid of 5hmC. Our data provide an overview of the genomic distribution of 5hmC in human brain and will set the stage for further functional characterization of this novel DNA modification.

| S-EPMC3130285 | biostudies-literature

Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates.

Project description:5-Hydroxymethylcytosine (hmC) was recently detected as the sixth base in mammalian tissue at so far controversial levels. The function of the modified base is currently unknown, but it is certain that the base is generated from 5-methylcytosine (mC). This fuels the hypothesis that it represents an intermediate of an active demethylation process, which could involve further oxidation of the hydroxymethyl group to a formyl or carboxyl group followed by either deformylation or decarboxylation. Here, we use an ultra-sensitive and accurate isotope based LC-MS method to precisely determine the levels of hmC in various mouse tissues and we searched for 5-formylcytosine (fC), 5-carboxylcytosine (caC), and 5-hydroxymethyluracil (hmU) as putative active demethylation intermediates. Our data suggest that an active oxidative mC demethylation pathway is unlikely to occur. Additionally, we show using HPLC-MS analysis and immunohistochemistry that hmC is present in all tissues and cell types with highest concentrations in neuronal cells of the CNS.

| S-EPMC3009720 | biostudies-literature

Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine.

Project description:In contrast to 5-methylcytosine (5-mC), which has been studied extensively, little is known about 5-hydroxymethylcytosine (5-hmC), a recently identified epigenetic modification present in substantial amounts in certain mammalian cell types. Here we present a method for determining the genome-wide distribution of 5-hmC. We use the T4 bacteriophage β-glucosyltransferase to transfer an engineered glucose moiety containing an azide group onto the hydroxyl group of 5-hmC. The azide group can be chemically modified with biotin for detection, affinity enrichment and sequencing of 5-hmC-containing DNA fragments in mammalian genomes. Using this method, we demonstrate that 5-hmC is present in human cell lines beyond those previously recognized. We also find a gene expression level-dependent enrichment of intragenic 5-hmC in mouse cerebellum and an age-dependent acquisition of this modification in specific gene bodies linked to neurodegenerative disorders.

| S-EPMC3107705 | biostudies-literature

Quantifying mammalian genomic DNA hydroxymethylcytosine content using solid-state nanopores.

Project description:5-hydroxymethylcytosine (5 hmC), the oxidized form of 5-methylcytosine (5 mC), is a base modification with emerging importance in biology and disease. However, like most epigenetic elements, it is transparent to many conventional genetic techniques and is thus challenging to probe. Here, we report a rapid solid-state nanopore assay that is capable of resolving 5 hmC with high specificity and sensitivity and demonstrate its utility in assessing global modification abundance in genomic DNA.

| S-EPMC4935868 | biostudies-literature

Transcriptome-wide distribution and function of RNA hydroxymethylcytosine

Project description:Our understanding of the posttranscriptional modifications that decorate RNA, a regulatory layer positioned between DNA and proteins, is in its infancy. Hydroxymethylcytosine, well described in DNA, occurs also in RNA, where its distribution, localization and function remain unexplored. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We provide the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We find that RNA hydroxymethylation can favor mRNA translation. Tet-deficient fruitflies show impaired brain development, accompanied by decreased RNA hydroxymethylation. Together, these steps into uncharted territory uncover central roles for RNA hydroxymethylation in Drosophila, highlighting the importance of epitranscriptomics.

2016-01-15 | GSE66090 | GEO

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