Hierarchical cooperation of transcription factors from integration analysis of DNA sequences, ChIP-Seq and ChIA-PET data

Xiaoyong Du,Yunlong Wang,Yaliang Zhang,Xueying Zhang,Ruimin Wang,Yaping Fang,Guoliang Li

doi:10.1186/s12864-019-5535-2

Xiaoyong Du, Yunlong Wang + Show 5 more

Open Access

https://doi.org/10.1186/s12864-019-5535-2

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Abstract

BackgroundChromosomal architecture, which is constituted by chromatin loops, plays an important role in cellular functions. Gene expression and cell identity can be regulated by the chromatin loop, which is formed by proximal or distal enhancers and promoters in linear DNA (1D). Enhancers and promoters are fundamental non-coding elements enriched with transcription factors (TFs) to form chromatin loops. However, the specific cooperation of TFs involved in forming chromatin loops is not fully understood.ResultsHere, we proposed a method for investigating the cooperation of TFs in four cell lines by the integrative analysis of DNA sequences, ChIP-Seq and ChIA-PET data. Results demonstrate that the interaction of enhancers and promoters is a hierarchical and dynamic complex process with cooperative interactions of different TFs synergistically regulating gene expression and chromatin structure. The TF cooperation involved in maintaining and regulating the chromatin loop of cells can be regulated by epigenetic factors, such as other TFs and DNA methylation.ConclusionsSuch cooperation among TFs provides the potential features that can affect chromatin’s 3D architecture in cells. The regulation of chromatin 3D organization and gene expression is a complex process associated with the hierarchical and dynamic prosperities of TFs.

Highlights

Chromosomal architecture, which is constituted by chromatin loops, plays an important role in cellular functions
Promoter–enhancer interaction analysis We developed the HidPET method to combine ChIA-PET and ChIP-Seq data with Protein-protein interaction (PPI) data to systematically study the hierarchy and dynamics of transcription factors (TFs) in four cell lines
This study provides a systematic approach to study the hierarchy and dynamics of TF cooperation in chromatin 3 dimension (3D) and Linear DNA (1D) space by using various data, such as the ChIA-PET, ChIP-Seq, and PPI data

Summary

Introduction

Chromosomal architecture, which is constituted by chromatin loops, plays an important role in cellular functions. Gene expression and cell identity can be regulated by the chromatin loop, which is formed by proximal or distal enhancers and promoters in linear DNA (1D). Wang et al BMC Genomics 2019, 20(Suppl 3):296 important role in gene regulation and disease [10], the specific mechanism, especially the involved molecules, such as proteins, and the cooperation of transcription factors (TFs) participating in the chromatin loop, remains poorly understood. Different combinations of TFs can result in various expression types in different tissues and specific expression types in different cell types and stages [13] These works reported many instances of cooperation between different TFs, only linear DNA sequence information and the co-localization of different proteins across the linear genome were considered. Substantial evidence indicates that different TFs can cooperate in 3D space and mediate interactions between distant sequences in the linear genome [5, 10, 15]

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