Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity

Colquitt, Bradley M.; Allen, William E.; Barnea, Gilad; Lomvardas, Stavros

doi:10.1073/pnas.1302759110

Cited by 103 publications

(114 citation statements)

References 35 publications

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“…11,12 Furthermore, evidence suggests that the 5hmC profile show a better correlation with gene expression compared to 5mC. 13 Zhang et al, 2014 reported a marked increase in total 5hmC levels in the heart and spleen of rats exposed to physiologically relevant levels of Arsenic (As) through drinking water. 14 An association between arsenic metabolism and global DNA hydroxymethylation has also been reported in humans.…”

Section: Introductionmentioning

confidence: 99%

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood

et al. 2015

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Section: Introductionmentioning

confidence: 99%

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood

et al. 2015

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“…Genomewide profiling revealed DNA methylation dynamics during neural lineage commitment, within which the change of 5hmC level was particularly significant [67,70]. DNA methylation dynamics correlates with the change of histone methylation, as well as the expression of related genes [12,70,83]. It is possible that different DNA methylation states are important to define cell identity.…”

Section: Resultsmentioning

confidence: 99%

“…Overexpression of Ezh2, a subunit of the Polycomb complex, which is responsible for the trimethylation of H3K27, or knockdown of Tet2 and Tet3, leads to defects in neural differentiation, suggesting that gain of 5hmC and loss of H3K27me3 cooperate to promote neurogenesis [70]. In another study, Colquitt et al developed genomic maps of 5hmC along the developmental lineage of the main olfactory epithelium -from multipotent stem cells through neuronal progenitors to mature olfactory sensory neurons (mOSNs) [83]. During mOSN development, 5hmC increases over gene bodies, particularly between the progenitor and mOSN stages.…”

Section: Dna Methylation Dynamics In Npc Differentiation Into Neuronsmentioning

confidence: 99%

“…Genes with high-level intragenic 5hmC showed a reduction of both 5hmC and expression level (such as Plxna1), and genes with moderate intragenic 5hmC showed an increase of 5hmC and expression level (such as Stxbp2). This change disrupted the normal molecular and anatomical features of the olfactory system [83]. Therefore, TET3 and its catalytic activity is crucial for the functional generation of mOSNs.…”

Section: Dna Methylation Dynamics In Npc Differentiation Into Neuronsmentioning

confidence: 99%

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DNA Methylation Dynamics in Neurogenesis

Wang

Tang

et al. 2016

Epigenomics

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Neurogenesis is not limited to the embryonic stage, but continually proceeds in the adult brain throughout life. Epigenetic mechanisms, including DNA methylation, histone modification and noncoding RNA, play important roles in neurogenesis. For decades, DNA methylation was thought to be a stable modification, except for demethylation in the early embryo. In recent years, DNA methylation has proved to be dynamic during development. In this review, we summarize the latest understanding about DNA methylation dynamics in neurogenesis, including the roles of different methylation forms (5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine), as well as their ‘writers’, ‘readers’ and interactions with histone modifications.

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“…The modification 5hmC is generally believed to be a gene activation mark for two reasons. First, it is enriched in active genes in brain and other tissues (5)(6)(7)(8)(9). Second, 5hmC is the key intermediate in the mammalian active DNA demethylation pathway in which 5hmC is further oxidized by TET to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) followed by removal of 5fC and 5caC through base excision repair (10)(11)(12).…”

Section: -Methylcytosinementioning

confidence: 99%

Simultaneous single-molecule epigenetic imaging of DNA methylation and hydroxymethylation

Song

Diao

Brunger

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the two major DNA epigenetic modifications in mammalian genomes and play crucial roles in development and pathogenesis. Little is known about the colocalization or potential correlation of these two modifications. Here we present an ultrasensitive single-molecule imaging technology capable of detecting and quantifying 5hmC and 5mC from trace amounts of DNA. We used this approach to perform single-molecule fluorescence resonance energy transfer (smFRET) experiments which measure the proximity between 5mC and 5hmC in the same DNA molecule. Our results reveal high levels of adjacent and opposing methylated and hydroxymethylated CpG sites (5hmC/5mCpGs) in mouse genomic DNA across multiple tissues. This identifies the previously undetectable and unappreciated 5hmC/5mCpGs as one of the major states for 5hmC in the mammalian genome and suggest that they could function in promoting gene expression.single-molecule imaging | epigenetics | 5-hydroxymethylcytosine | 5-methylcytosineE pigenetic modifications of DNA contribute critical regulatory functions to the underlining genetic sequence. The two major DNA modifications in the mammalian genome are 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), which are often referred to as the "fifth base" and "sixth base," respectively; 5mC is generated by DNA methyltransferase (DNMTs) mainly at CpG dinucleotides and generally results in gene silencing (1, 2), and 5hmC is oxidized from 5mC by ten-eleven translocation (TET) family dioxygenases and mostly enriched in brain (3, 4). The modification 5hmC is generally believed to be a gene activation mark for two reasons. First, it is enriched in active genes in brain and other tissues (5-9). Second, 5hmC is the key intermediate in the mammalian active DNA demethylation pathway in which 5hmC is further oxidized by TET to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) followed by removal of 5fC and 5caC through base excision repair (10-12).Intensive research on 5hmC in recent years indicated the TET-mediated oxidation process plays important roles in diverse biological processes ranging from embryonic development to carcinogenesis; however, how 5hmC exerts its biological role is largely unclear (13-15). One important piece of information that has been missing is the interplay between 5hmC and its precursor 5mC. Despite many techniques that have been developed to detect and sequence 5mC and 5hmC, including recent advances in base-resolution mapping of 5hmC (16), no method to date can simultaneously reveal 5mC and 5hmC sites in the same DNA molecule. Here we present an ultrasensitive single-molecule imaging technology capable of detecting and quantifying 5mC and 5hmC from trace samples, which we used to study the distance relationship between 5mC and 5hmC with single-molecule fluorescence resonance energy transfer (smFRET). Results and DiscussionOur imaging approach uses a selective chemical labeling strategy (17) to label DNA base modifications wi...

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Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity

Cited by 103 publications

References 35 publications

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood

DNA Methylation Dynamics in Neurogenesis

Simultaneous single-molecule epigenetic imaging of DNA methylation and hydroxymethylation

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