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Genome-wide atlas of gene enhancers in the brain online
Date:1/31/2013

ncers, sequences of DNA that act to amplify the expression of a specific gene. Characterizing gene enhancers tends to be difficult because an enhancer does not have to be located directly adjacent to the gene it is enhancing, but can in fact be located hundreds of thousands of DNA basepairs away.

"In addition to acting over long distances and being located upstream, downstream or in introns of protein-coding genes, the sequence features of gene enhancers are poorly understood," Visel says. "However, gene-centric studies have provided strong evidence that gene enhancers are critical for normal embryonic development of the brain and have also linked human diseases to perturbed enhancer sequences."

Visel and an international team of researchers met the challenges of systematic identification and functional characterization of gene enhancers in the cerebrum through a combination of ChIP-seq studies and large-scale histological analyses in transgenic mice, in which the activity patterns of human telencephalon enhancers can be studied. ChIP-seq, which stands for "chromatin immunoprecipitation followed by sequencing," is a technique for genome-wide profiling of proteins that interact with DNA.

This combination of approaches enabled Visel and his colleagues to identify over 4,600 candidate embryonic forebrain enhancers. Furthermore, studying mouse embryos they mapped the activity of 145 of these enhancers at high resolution to define where exactly in the developing brain they drive the expression of their respective target genes. The result is a comprehensive, electronically accessible database for investigating the gene regulatory mechanisms of cerebrum development, and for studying the roles of distant-acting enhancers in neurodevelopmental disorders.

"By mapping hundreds of gene enhancer sequences and defining where exactly in the developing brain they are active, our enhancer atlas provides important information to connect non-coding
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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