Genomic antagonism between retinoic acid and estrogen signaling in breast cancer
Cell. 2009 Jun 26;137(7):1259-71.
Institute for Genomics and Systems Biology and Department of Human Genetics, The University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
Retinoic acid (RA) triggers antiproliferative effects in tumor cells, and therefore RA and its synthetic analogs have great potential as anticarcinogenic agents. Retinoic acid receptors (RARs) mediate RA effects by directly regulating gene expression. To define the genetic network regulated by RARs in breast cancer, we identified RAR genomic targets using chromatin immunoprecipitation and expression analysis. We found that RAR binding throughout the genome is highly coincident with estrogen receptor alpha (ERalpha) binding, resulting in a widespread crosstalk of RA and estrogen signaling to antagonistically regulate breast cancer-associated genes. ERalpha- and RAR-binding sites appear to be coevolved on a large scale throughout the human genome, often resulting in competitive binding activity at nearby or overlapping cis-regulatory elements. The highly coordinated intersection between these two critical nuclear hormone receptor signaling pathways provides a global mechanism for balancing gene expression output via local regulatory interactions dispersed throughout the genome.
Research Papers
- Genome-wide Association of Yorkie with Chromatin and Chromatin-Remodeling Complexes
- CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia
- Integrative eQTL-Based Analyses Reveal the Biology of Breast Cancer Risk Loci
- Robust and tunable circadian rhythms from differentially sensitive catalytic domains
- A cis-regulatory map of the Drosophila genome
- Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis
- Adaptive evolution and the birth of CTCF binding sites in the Drosophila genome
- A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult
- Orderly wheels of the cyanobacterial clock
- Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signaling networks
