Effects of DNA Methylation on TFs in Human Embryonic Stem Cells
Autor: | Yixiao Zhai, Tianjiao Zhang, Guohua Wang, Ximei Luo, Shumei Zhang, Fang Wang |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Regulation of gene expression
DNA methylation lcsh:QH426-470 Bisulfite sequencing Methylation Biology CTCF Cell biology chemistry.chemical_compound lcsh:Genetics H1-hESC chemistry transcription factors Genetics CEBPB Molecular Medicine natural sciences Binding site Enhancer Genetics (clinical) DNA Original Research |
Zdroj: | Frontiers in Genetics, Vol 12 (2021) Frontiers in Genetics |
ISSN: | 1664-8021 |
DOI: | 10.3389/fgene.2021.639461/full |
Popis: | DNA methylation is an important epigenetic mechanism for gene regulation. The conventional view of DNA methylation is that DNA methylation could disrupt protein-DNA interactions and repress gene expression. Several recent studies reported that DNA methylation could alter transcription factors (TFs) binding sequence specificity in vitro. Here, we took advantage of the large sets of ChIP-seq data for TFs and whole-genome bisulfite sequencing data in many cell types to perform a systematic analysis of the protein-DNA methylation in vivo. We observed that many TFs could bind methylated DNA regions, especially in H1-hESC cells. By locating binding sites, we confirmed that some TFs could bind to methylated CpGs directly. The different proportion of CpGs at TF binding specificity motifs in different methylation statuses shows that some TFs are sensitive to methylation and some could bind to the methylated DNA with different motifs, such as CEBPB and CTCF. At the same time, TF binding could interactively alter local DNA methylation. The TF hypermethylation binding sites extensively overlap with enhancers. And we also found that some DNase I hypersensitive sites were specifically hypermethylated in H1-hESC cells. At last, compared with TFs’ binding regions in multiple cell types, we observed that CTCF binding to high methylated regions in H1-hESC were not conservative. These pieces of evidence indicate that TFs that bind to hypermethylation DNA in H1-hESC cells may associate with enhancers to regulate special biological functions. |
Databáze: | OpenAIRE |
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