Beijing Institute of Radiation Medicine, Beijing 100850, China.
Bioinformatics. 2017 Sep 1;33(17):2611-2614. doi: 10.1093/bioinformatics/btx282.
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.
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.
ylu.phd@gmail.com or boxc@bmi.ac.cn.
Supplementary data are available at Bioinformatics online.
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。
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。
ylu.phd@gmail.com 或 boxc@bmi.ac.cn。
补充数据可在“生物信息学”在线获取。