Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome

By Miao Yu, Gary Chung Hon, Keith E. Szulwach, Chun-Xiao Song, Liang Zhang, Audrey Kim, Xuekun Li, Qing Dai, Beomseok Park, Jung-Hyun Min and 3 more. 2012

1,020 citations recorded by the source corpus.

SUMMARY The study of 5-hydroxylmethylcytosines (5hmC) has been hampered by the lack of a method to map it at single-base resolution on a genome-wide scale. Affinity purification-based methods cannot precisely locate 5hmC nor accurately determine its relative abundance at each modified site. We here present a genome-wide approach, Tet-assisted Bisulfite Sequencing (TAB-Seq), for mapping 5hmC at base resolution and quantifying the relative abundance of 5hmC as well as 5mC when combined with traditional bisulfite sequencing. Application of this method to embryonic stem cells not only confirms widespread distribution of 5hmC in the mammalian genome, but also reveals sequence bias and strand asymmetry at 5hmC sites. We observe high levels of 5hmC and reciprocally low levels of 5mC near but not on transcription factor binding sites. Additionally, the relative abundance of 5hmC varies significantly among distinct functional sequence elements, suggesting different mechanisms for 5hmC deposition and maintenance.

Subfields: Molecular Biology

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Citations in the corpus

Impact of cytosine methylation on DNA binding specificities of human transcription factors (2017, neutral): “is unlikely that the effects observed in this study were due to loss of this modified base, because it is present at low per-allele frequency (53), and the differences in OCT4 binding to CpG-containing motifs were also observed in comparisons between the Dnmt-TKO and wild-type cell lines (fig.”
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, neutral): “Interestingly, base-resolution mapping indicates that 5hmC is actually depleted at the binding motif of transcription factors or CTCF insulators but enriched at immediately adjacent regions (Lister et al., 2013; Yu et al., 2012).”
Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain (2015, background): “Furthermore, at non-CG sites in these two DMVs, we find that essentially all of the observed hyper-methylation originates frommCH, consistent with evidence that hydroxymethylation occurs nearly exclusively in the CG context (Yu et al., 2012).”
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes (2013, neutral): “In Th cells, a super-enhancer is associated with the gene Tcf7 that encodes T cell factor 1 (Tcf-1), which is critical for the production of T cells during hematopoiesis (Staal and Sen, 2008; Xue and Zhao, 2012; Yu et al., 2012b).”
Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence (2014, neutral): “, strand-biased DNA modification) (Yu et al. 2012), then the number of different states could swell to 25(2) (or 625).”
Global Epigenomic Reconfiguration During Mammalian Brain Development (2013, methodology): “This modification appears to be restricted to the CG context, as also observed in human and mouse ES cells (34); after correction for false detection, we estimated that 0.”
Modification of enhancer chromatin: what, how and why? (2013, background): “…being tightly linked to enhancer activity, H3K4me1 perhaps broadly defines (or merely correlates with) a ‘‘window of opportunity’’ within which enhancer activation can occur, for example through facilitating nucleosomal mobility and/or binding of pioneer TFs (Zaret and Carroll, 2011) (Figure 1B).”