Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2
Name
Bochkis-2012-Genome-Wide Location.pdf
Size
1.1 MB
Format
Adobe PDF
Checksum (MD5)
4a539d074318f8802c62ddd62c864083
Author(s)
Bochkis, Irina M.
Schug, Jonathan
Ye, Diana Z.
Kurinna, Svitlana
Stratton, Sabrina A.
Barton, Michelle C.
Kaestner, Klaus H.
Date Issued
June 2012
Journal
PLoS Genetics
Publisher
Public Library of Science
Citation
Bochkis, Irina M. et al. “Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2.” Ed. Michael Snyder. PLoS Genetics 8.6 (2012): e1002770.
Version
Final published version
Abstract
Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution.
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pgen.1002770
