MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
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...hmC accumulates during early postnatal brain development in mice (31, 32), becoming enriched in highly expressed genes (33)....
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...Overall, transcriptional activity is associated with intragenic hmCG enrichment, as reported (33), with in utero establishment of adult hmCG patterns for cell type–specific genes and loss of hmC enrichment associated with developmentally coupled transcriptional down-regulation....
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...These constitutively highly expressed genes enriched for neuronal function also show extensive intragenic mCH hypomethylation in neurons in contrast to glia (box 3), and they are enriched for hmCG (box 4) as previously described (32, 33)....
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...Our base-resolution analysis of hmC using TAB-Seq revealed that intragenic and global hmCG levels are largely equivalent between chromosomes, whereas hmCG/CG is 22% lower on the male ChrX, consistent with previous reports from enrichment based detection of hmC (32, 33) (Fig....
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Cites background from "MeCP2 binds to 5hmc enriched within..."
...…binding of Uhrf2 to hmC, suggesting specific biological roles for mC and hmC. Oxidized derivatives of mC recruit distinct transcription regulators as well as a large number of DNA repair proteins in mouse ES cells, implicating the DNA damage response as a major player in active DNA demethylation....
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References
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"MeCP2 binds to 5hmc enriched within..." refers methods in this paper
...To identify these factors, nuclear extracts prepared from rodent brain (Klose and Bird, 2004) were incubated with magnetic beads coated with DNA containing unmodified C, 5mC, or 5hmC DNA in the presence of excess of nonspecific DNA competitor, followed by isolation of the beads and visualization of proteins after elution and SDSPAGE....
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...To identify these factors, nuclear extracts prepared from rodent brain (Klose and Bird, 2004) were incubated with magnetic beads coated with DNA containing unmodified C, 5mC, or 5hmC DNA in the presence of excess of nonspecific DNA competitor, followed by isolation of the beads and visualization of…...
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89 citations
"MeCP2 binds to 5hmc enriched within..." refers background in this paper
...…been shown to occur in response to a variety 1424 Cell 151, 1417–1430, December 21, 2012 ª2012 Elsevier Inc. of stimuli (Chen et al., 2003; Tao and Wu, 2009; Rutlin and Nelson, 2011; Adkins and Georgel, 2011; Gonzales et al., 2012) could alter its substrate specificity and downstream functions....
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...…proteins that bind them vary in each cell type, the phenotypic consequences of changes in the function of MeCP2, whether as a result of mutation (Adkins and Georgel, 2011; Tao andWu, 2009; Amir et al., 1999) or posttranslational modification (Rutlin and Nelson, 2011; Gonzales et al., 2012),…...
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...Because the levels of 5hmC and 5mC and the proteins that bind them vary in each cell type, the phenotypic consequences of changes in the function of MeCP2, whether as a result of mutation (Adkins and Georgel, 2011; Tao andWu, 2009; Amir et al., 1999) or posttranslational modification (Rutlin and Nelson, 2011; Gonzales et al....
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...of stimuli (Chen et al., 2003; Tao and Wu, 2009; Rutlin and Nelson, 2011; Adkins and Georgel, 2011; Gonzales et al., 2012) could alter its substrate specificity and downstream functions....
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89 citations
"MeCP2 binds to 5hmc enriched within..." refers background in this paper
..., 1999) or posttranslational modification (Rutlin and Nelson, 2011; Gonzales et al., 2012), will be cell type and circuit specific....
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...…been shown to occur in response to a variety 1424 Cell 151, 1417–1430, December 21, 2012 ª2012 Elsevier Inc. of stimuli (Chen et al., 2003; Tao and Wu, 2009; Rutlin and Nelson, 2011; Adkins and Georgel, 2011; Gonzales et al., 2012) could alter its substrate specificity and downstream functions....
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...…each cell type, the phenotypic consequences of changes in the function of MeCP2, whether as a result of mutation (Adkins and Georgel, 2011; Tao andWu, 2009; Amir et al., 1999) or posttranslational modification (Rutlin and Nelson, 2011; Gonzales et al., 2012), will be cell type and circuit specific....
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...of stimuli (Chen et al., 2003; Tao and Wu, 2009; Rutlin and Nelson, 2011; Adkins and Georgel, 2011; Gonzales et al., 2012) could alter its substrate specificity and downstream functions....
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70 citations
"MeCP2 binds to 5hmc enriched within..." refers result in this paper
...This is consistent with the analysis of individual genes shown in Figure 7A, and confirms previous studies demonstrating that the 5mC-enriched DNA is present MNase-resistant compact structures (Karymov et al., 2001)....
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59 citations
"MeCP2 binds to 5hmc enriched within..." refers background in this paper
...However, the observations that in brain nuclei a large fraction of MeCP2 is localized within highly nuclease accessible regions (Thambirajah et al., 2012), that loss of MeCP2 can lead to downregulation of expressed genes (Ben-Shachar et al....
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...Given the high abundance of MeCP2 in the brain (Figure S4B) (Guy et al., 2001; Skene et al., 2010; Thambirajah et al., 2012), andourdemonstration thatMeCP2bindsavidly to 5hmCcontainingDNA in vitro, wewere next interested in assessing its potential role in global regulation of chromatin…...
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...For example, it has recently been shown that two populations of MeCP2 are present in the brain: one in chromatin regions that are enriched in nucleosomes, and the other that is loosely bound to highly accessible chromatin domains (Thambirajah et al., 2012)....
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...Given the high abundance of MeCP2 in the brain (Figure S4B) (Guy et al., 2001; Skene et al., 2010; Thambirajah et al., 2012), andourdemonstration thatMeCP2bindsavidly to 5hmCcontainingDNA in vitro, wewere next interested in assessing its potential role in global regulation of chromatin accessibility....
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...However, the observations that in brain nuclei a large fraction of MeCP2 is localized within highly nuclease accessible regions (Thambirajah et al., 2012), that loss of MeCP2 can lead to downregulation of expressed genes (Ben-Shachar et al., 2009; this study), and that 5hmC is enriched in the gene…...
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