Abstract
Regulation of gene expression in time, space and quantity is orchestrated by the functional interplay of cis-acting elements and trans-acting factors. Our current view postulates that transcription factors recognize enhancer DNA and read the transcriptional regulatory code by cooperative DNA binding to specific DNA motifs, thus instructing the recruitment of transcriptional regulatory complexes forming a plethora of higher-ordered multi-protein-DNA and protein-protein complexes. Here, we reviewed the formation of multi-dimensional chromatin assemblies implicated in gene expression with emphasis on the regulatory role of enhancer hubs as coordinators of stochastic gene expression. Enhancer hubs contain many interacting regulatory elements and represent a remarkably dynamic and heterogeneous network of multivalent interactions. A functional consequence of such complex interaction networks could be that individual enhancers function synergistically to ensure coordination, tight control and robustness in regulation of expression of spatially connected genes. In this review, we discuss fundamental paradigms of such inter- and intra- chromosomal associations both in the context of immune-related genes and beyond.
Highlights
Reviewed by: Chris Benner, University of California, San Diego, United States Wing Fuk Chan, Walter and Eliza Hall Institute of Medical Research, Australia
Our current view postulates that transcription factors recognize enhancer DNA and read the transcriptional regulatory code by cooperative DNA binding to specific DNA motifs, instructing the recruitment of transcriptional regulatory complexes forming a plethora of higher-ordered multi-protein-DNA and protein-protein complexes
Cells respond to signals by engaging various receptors that recognize and interpret the environment by initiating signal transduction cascades, culminating in the activation of transcription factors (TFs), which bind to specific regulatory DNA sequences to control the expression of genes, orchestrating a dynamic interplay between genome form and function [3,4,5,6]
Summary
Enhancers and promoters represent the major classes of DNA regulatory elements responsible for warranting the execution of precise gene expression programs by functioning as information processing units interpreting the extra- and intra-cellular signals in the form of transcription factor binding events, which are followed by the recruitment of various transcriptional regulatory proteins such as cofactors, chromatin modifiers
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