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利用 Hi-C 数据探索空间相邻的 TFBS 聚集区。

Exploring spatially adjacent TFBS-clustered regions with Hi-C data.

机构信息

Beijing Institute of Radiation Medicine, Beijing 100850, China.

出版信息

Bioinformatics. 2017 Sep 1;33(17):2611-2614. doi: 10.1093/bioinformatics/btx282.

Abstract

MOTIVATION

Transcription factor binding sites (TFBSs) are clustered in the human genome, forming the TFBS-clustered regions that regulate gene transcription, which requires dynamic chromatin configurations between promoters and distal regulatory elements. Here, we propose a regulatory model called spatially adjacent TFBS-clustered regions (SATs), in which TFBS-clustered regions are connected by spatial proximity as identified by high-resolution Hi-C data.

RESULTS

TFBS-clustered regions forming SATs appeared less frequently in gene promoters than did isolated TFBS-clustered regions, whereas SATs as a whole appeared more frequently. These observations indicate that multiple distal TFBS-clustered regions combined to form SATs to regulate genes. Further examination confirmed that a substantial portion of genes regulated by SATs were located between the paired TFBS-clustered regions instead of the downstream. We reconstructed the chromosomal conformation of the H1 human embryonic stem cell line using the ShRec3D algorithm and proposed the SAT regulatory model.

CONTACT

ylu.phd@gmail.com or boxc@bmi.ac.cn.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

转录因子结合位点 (TFBS) 在人类基因组中聚集,形成调节基因转录的 TFBS 聚集区,这需要启动子和远端调节元件之间的动态染色质构象。在这里,我们提出了一个称为空间相邻 TFBS 聚集区 (SATs) 的调控模型,其中 TFBS 聚集区通过高分辨率 Hi-C 数据识别的空间接近性连接。

结果

形成 SATs 的 TFBS 聚集区在基因启动子中出现的频率低于孤立的 TFBS 聚集区,而 SATs 整体出现的频率更高。这些观察表明,多个远端 TFBS 聚集区组合形成 SATs 来调节基因。进一步的检查证实,由 SATs 调节的大量基因位于配对的 TFBS 聚集区之间,而不是下游。我们使用 ShRec3D 算法重建了 H1 人胚胎干细胞系的染色体构象,并提出了 SAT 调控模型。

联系方式

ylu.phd@gmail.comboxc@bmi.ac.cn

补充信息

补充数据可在“生物信息学”在线获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f94c/5860062/8f645b507cd1/btx282f1.jpg

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