Nature Journal Club

Marcelo Nobrega

University of Chicago, Illinois

A human geneticist explores the ways that genes are regulated.

Gene expression is the cellular process that decodes the genetic information in DNA and converts it into proteins. It is regulated at many levels: when messenger RNA is transcribed from DNA; when mRNA is translated into proteins; and at the epigenetic level, when the structure of chromatin, coils of DNA wound around histone proteins, is altered. Although most discussion of gene expression focuses on the regulation of transcription, the other components of the process are also crucial. Yet little is known about how they are integrated.

Work by Tom Misteli at the National Cancer Institute in Bethesda, Maryland, and his team provides a striking example of the integration of seemingly disparate components in gene-expression regulation (R. F. Luco et al. Science 327, 996–1000; 2010). They describe how patterns of alternative splicing of newly made RNA, a key regulatory mechanism, can themselves be regulated by specific chemical modifications in the chromatin. They also found that a given set of modifications to histones predicts patterns of RNA splicing. The authors conservatively estimate that this mechanism occurs in dozens to hundreds of genes in the human genome.

This remarkable study makes a connection between a quintessential transcription-regulation mechanism, histone modification, and a post-transcriptional process, alternative splicing. It shows that chromatin can regulate not only how much of a protein, but also which protein, is made in a cell.

We have seen a surge of intriguing studies suggesting that molecules that were thought to regulate transcription also direct epigenetic modifications, modify alternative-splicing patterns and participate in the intracellular transport of RNA. These findings and the work of Misteli and colleagues provide insight into how the components of gene regulation are integrated.

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