Extensive Promoter-centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

By Guoliang Li, Xiaoan Ruan, Raymond K. Auerbach, K. Sandhu, Meizhen Zheng, Ping Wang, H. Poh, Yufen Goh, Joanne Lim, Jingyao Zhang and 26 more. 2012

1,231 citations recorded by the source corpus.

Summary Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intra-genic, extra-genic and inter-genic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated non-coding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into the transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells.

Subfields: Molecular Biology

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Citations in the corpus

Iterative random forests to discover predictive and stable high-order interactions (2017, background): “In addition to the high predictive accuracy of RFs, the decision tree base learner captures the underlying biology of local, combinatorial interactions (21), an important feature for biological data, where a single molecule often performs many roles in various cellular contexts.”
Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers (2014, neutral): “3D chromatin links bridging different initiation regions have been observed both between traditional enhancers and promoters and between pairs of promoters 33 .”
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants (2013, background): “Additionally, we demonstrate that three of three SNPs previously shown to alter long-range enhancer function [rs12740374/ SORT1 (18) and rs6983267/MYC (19, 20)] or to reside in a longrange contact point [rs7578326/IRS1 (21)] overlap a stretch enhancer specifically in the relevant cell type(s) (SI Ap”
CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. (2015, background): “…(ChIP), ChIA-PET is unique in detecting protein factor-mediated chromatin interactions and is capable of generating high-resolution ( 100 bp) genome-wide chromatin interaction maps with binding-site specificity among functional elements in human and mouse (Li et al., 2012; Zhang et al., 2013).”
Systematic mapping of functional enhancer-promoter connections with CRISPR interference (2016, background): “It remains unclear how many regulatory elements control any given gene, or how many genes are regulated by any given element (2, 3, 8).”
Predicting enhancer-promoter interaction from genomic sequence with deep neural networks (2016, background): “Indeed, the mappings of global chromatin interaction based on Hi-C and ChIA-PET have shown that a significant proportion of enhancer elements skip nearby genes and interact with promoters further away in the genome by forming long-range chromatin loops [8, 9].”
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes (2014, positive): “SMC1 ChIA-PET was performed as previously described (Chepelev et al., 2012; Fullwood et al., 2009; Goh et al., 2012; Li et al., 2012).”