December 2013

Long-distance relationships in gene regulation

Cover of the Dec. 6, 2013, issue of The Journal of Biological ChemistryIn a recent minireview in The Journal of Biological Chemistry, Zong Wei and colleagues at the University of Southern California give an extensive account of the significance and biological implications of long-range chromosomal interactions.

The human genome has more than 20,000 genes distributed across 22 pairs of autosomes and two sex chromosomes. Regulation of gene expression is critical for efficient functioning of a cell, be it developmental processes or stress adaptations. The chromosomal organization in the nucleus follows a hierarchal system ranging from nucleosomes to higher-order chromatin fibers. This organization modulates chromosomal condensation, which plays a pivotal role in gene transcription by masking the transcription-factor-specific regulatory sequences.
The classical perception of transcriptional gene activation involves a one-dimensional model of binding of transcription factors to specific regulatory sequences followed by RNAP and associated factor recruitment to drive the process. The advent of novel chromosome-capture techniques has revolutionized the field of long-range chromosomal interactions between regulatory elements across the genome during transcription, enabling a three-dimensional approach.
The JBC minireview authors discuss the evolution of the state-of-the-art techniques used to study the long-range interactions ranging from fluorescent in situ hybridization to powerful chromosome-capture methods. While highlighting the technical details, the authors compare the applications of chromosome conformation capture, chromosome capture-on-chip and chromosome conformation capture carbon copy, known as 3C, 4C and 5C, respectively.
Subsequently, the minireview delves into the fascinating concept of transcription factories, wherein genes as far as 40 MBs away share the same transcriptional foci, reiterating the principle of long-range interactions. Additionally, the authors highlight the application of the chromosome-capture techniques to identify these transcription factories. The minireview concludes with an explanation of the ubiquitous nature of long-range interactions in fundamental physiological processes, such as chromosome translocation, nuclear organization and X chromosome inactivation.
This minireview, titled “The biological implications and regulatory mechanisms of long-range chromosomal interactions,” outlines the significance of the current research in the field, helping readers to gain an appreciation of the extremely dynamic nature of chromatin, which loops within the intra- and internuclear compartments to regulate fundamentally important cellular processes.


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