An oestrogen-receptor-α-bound human chromatin interactome

Abstract

Genomes are organized into high-level 3-dimensional structures, and DNA elements separated by long genomic distances could functionally interact. Many transcription factors bind to regulatory DNA elements distant from gene promoters. While distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Therefore, we developed Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) for de novo detection of global chromatin interactions, and comprehensively mapped the chromatin interaction network bound by oestrogen receptor α (ERα) in the human genome. We found that most high-confidence remote ERα binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

“…Indeed, it is highly difficult to confidently assess the relationship between enhancer regions and the genes they control (Heintzman and Ren, 2009). It is likely, however, that these issues will be resolved once the architecture of more miRNA loci gets mapped in detail and novel experimental techniques such as Chromosome Conformation Capture methodologies are utilized to determine long-range chromosomal interactions between distal cis-regulatory elements and target promoters (Fullwood et al, 2009;Heintzman and Ren, 2009). Regardless, it may well be expected that additional Wnt-responsive miRNAs remains to be identified because of the context-specificity of Wnt signaling and the existence of miRNAs not detected by the TaqMan Array MicroRNA Cards.…”

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…Using the circular chromosome conformation capture method, multiple ERα binding sites have been shown to interact with classical ERα target genes [e.g., pS2/TFF1, GREB1, carbonic anhydrase 12 (CA12), and B cell lymphoma 2] via looping to regulate transcription [21][22][23]. Fullwood et al [24] mapped the chromatin interaction network bound to ERα in the human genome by utilizing chromatin interaction analysis by paired end-tag sequencing and discovered that most high-confidence ERα-binding sites are anchored to gene promoters through long-range chromatin interactions like looping. Similar three-dimensional chromatin interaction studies using tissue samples from cancer patients reveal that the clinical outcome of breast cancers is decided at the level of chromatin interaction by ERα [25].…”

Infrastructure for genomic interactions: Bioconductor classes for Hi-C, ChIA-PET and related experiments

“…Techniques such as chromatin conformation capture with high-throughput sequencing (Hi-C) 1 and chromatin interaction analysis with paired-end tags (ChIA-PET) 2 are increasingly being used to study the three-dimensional structure and organisation of the genome. Briefly, genomic DNA is fragmented and subjected to a ligation step during which DNA from interacting loci are ligated together.…”