预测人类细胞发育过程中与DNA去甲基化相关的转录因子。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2022-03-01 Epub Date: 2022-02-10 DOI:10.1007/s10577-022-09685-6
Yurina Miyajima, Shuhei Noguchi, Yuki Tanaka, Jing-Ru Li, Hajime Nishimura, Mami Kishima, Joanne Lim, Erina Furuhata, Takahiro Suzuki, Takeya Kasukawa, Harukazu Suzuki
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引用次数: 2

摘要

CpG二核苷酸的DNA甲基化是一种重要的表观遗传修饰,参与哺乳动物基因表达的调控,每种类型的细胞在分化过程中都有特定的甲基化谱。最近,研究表明,一小部分转录因子(TFs)可能在其结合位点促进DNA去甲基化。我们开发了一个生物信息学管道,从全基因组DNA甲基化数据中预测在其结合位点促进DNA去甲基化的tf。我们将该管道应用于国际人类表观基因组联盟甲基组数据,并选择了393个候选转录因子结合基序和相关的383个可能与DNA去甲基化相关的tf。使用体外实验验证候选TF的一个子集表明,来自不同TF家族的49个TF中有28个具有dna去甲基化促进活性;TF家族,如bHLH和ETS,既包含有活性的TF,也包含没有活性的TF。鉴定的tf显示出较大的去甲基化/甲基化CpG比率,并且它们的去甲基化CpG在原始细胞中显示出明显的高甲基化倾向。此外,鉴定出的TF促进了不同CpGs组的去甲基化,TF家族成员之间的目标CpGs略有重叠,这与鉴定出的TF的基因本体(GO)术语分析结果一致。基因表达分析表明,来自不同家族的多个tf在人体细胞和组织中特异性表达。总之,我们的研究结果表明,在人类细胞发育过程中,来自不同TF家族的大量TF与细胞类型特异性DNA去甲基化有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Prediction of transcription factors associated with DNA demethylation during human cellular development.

Prediction of transcription factors associated with DNA demethylation during human cellular development.

Prediction of transcription factors associated with DNA demethylation during human cellular development.

Prediction of transcription factors associated with DNA demethylation during human cellular development.

DNA methylation of CpG dinucleotides is an important epigenetic modification involved in the regulation of mammalian gene expression, with each type of cell developing a specific methylation profile during its differentiation. Recently, it has been shown that a small subgroup of transcription factors (TFs) might promote DNA demethylation at their binding sites. We developed a bioinformatics pipeline to predict from genome-wide DNA methylation data TFs that promote DNA demethylation at their binding site. We applied the pipeline to International Human Epigenome Consortium methylome data and selected 393 candidate transcription factor binding motifs and associated 383 TFs that are likely associated with DNA demethylation. Validation of a subset of the candidate TFs using an in vitro assay suggested that 28 of 49 TFs from various TF families had DNA-demethylation-promoting activity; TF families, such as bHLH and ETS, contained both TFs with and without the activity. The identified TFs showed large demethylated/methylated CpG ratios and their demethylated CpGs showed significant bias toward hypermethylation in original cells. Furthermore, the identified TFs promoted demethylation of distinct sets of CpGs, with slight overlap of the targeted CpGs among TF family members, which was consistent with the results of a gene ontology (GO) term analysis of the identified TFs. Gene expression analysis of the identified TFs revealed that multiple TFs from various families are specifically expressed in human cells and tissues. Together, our results suggest that a large number of TFs from various TF families are associated with cell-type-specific DNA demethylation during human cellular development.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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