Enhancer-promoter communication and transcriptional regulation of Igh

Program in Immunology, Department of Pathology, Tufts University School of Medicine, Boston, MA, USA.
Trends in Immunology (Impact Factor: 10.4). 08/2011; 32(11):532-9. DOI: 10.1016/
Source: PubMed


Transcriptional regulation of eukaryotic protein-coding genes requires the participation of site-specific transcription factors that bind distal regulatory elements, as well as factors that, together with RNA polymerase II, form the basal transcription machinery at the core promoter. Gene regulation requires proper communication between promoters and enhancers, often over great distances. Therefore, it is important to understand the potentially inter-related transcription factor interactions at both of these elements. How this is achieved on tissue-specific genes, such as the immunoglobulin heavy chain (IgH) in B cells remains unclear. Here, we review known interactions at the Igh variable region (V(H)) promoters and present our perspective on promoter-enhancer interactions that are likely important for Ig gene regulation in B cells.

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Available from: Ananda L Roy
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    • "Taking into account the fact that the gene regulatory regions in the majority of cases house multitude of sites for various TFs [60]; [61]; [62], we assumed that local clustering of ChIP-seq peaks for different TFs in a certain genomic region could suggest its regulatory significance. In this work, we have used the data obtained under the international ENCODE project on the distribution of binding sites for 134 TFs in the human genome (2.75 million ChIP-seq peaks). "
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    ABSTRACT: A vast amount of SNPs derived from genome-wide association studies are represented by non-coding ones, therefore exacerbating the need for effective identification of regulatory SNPs (rSNPs) among them. However, this task remains challenging since the regulatory part of the human genome is annotated much poorly as opposed to coding regions. Here we describe an approach aggregating the whole set of ENCODE ChIP-seq data in order to search for rSNPs, and provide the experimental evidence of its efficiency. Its algorithm is based on the assumption that the enrichment of a genomic region with transcription factor binding loci (ChIP-seq peaks) indicates its regulatory function, and thereby SNPs located in this region are more likely to influence transcription regulation. To ensure that the approach preferably selects functionally meaningful SNPs, we performed enrichment analysis of several human SNP datasets associated with phenotypic manifestations. It was shown that all samples are significantly enriched with SNPs falling into the regions of multiple ChIP-seq peaks as compared with the randomly selected SNPs. For experimental verification, 40 SNPs falling into overlapping regions of at least 7 TF binding loci were selected from OMIM. The effect of SNPs on the binding of the DNA fragments containing them to the nuclear proteins from four human cell lines (HepG2, HeLaS3, HCT-116, and K562) has been tested by EMSA. A radical change in the binding pattern has been observed for 29 SNPs, besides, 6 more SNPs also demonstrated less pronounced changes. Taken together, the results demonstrate the effective way to search for potential rSNPs with the aid of ChIP-seq data provided by ENCODE project.
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    • "These interactions are essential for looping as silencing of either OCA-B or TFII-I results in disruption of the loop formation and IgH transcription (Ren et al., 2011). Thus, TFII-I plays an important role in establishing enhancer-promoter communication during IgH transcriptional regulation (Ren et al., 2011; Roy et al., 2011). "
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    ABSTRACT: Exactly twenty years ago TFII-I was discovered as a biochemical entity that was able to bind to and function via a core promoter element called the Initiator (Inr). Since then several different properties of this signal-induced multifunctional factor were discovered. Here I update these ever expanding functions of TFII-I--focusing primarily on the last ten years since the first review appeared in this journal.
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