A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans.
We examined how a p53 enhancer transmits regulatory information in vivo. Using genetic ablation together with digital chromosome conformation capture and fluorescent in situ hybridization, we found that a Drosophila p53 enhancer region (referred to as the p53 response element [p53RE]) physically contacts targets in cis and across the centromere to control stress-responsive transcription at these sites. Furthermore, when placed at ectopic genomic positions, fragments spanning this element re-established chromatin contacts and partially restored target gene regulation to mutants lacking the native p53RE. Therefore, a defined p53 enhancer region is sufficient for long-range chromatin interactions that enable multigenic regulation.
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nichole
N
Link
Paula
P
Kurtz
Melissa
M
O'Neal
Gianella
G
Garcia-Hughes
John M
JM
Abrams
D000818:Animals; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D011485:Protein Binding; D013312:Stress, Physiological / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D002843:Chromatin; D016159:Tumor Suppressor Protein p53
apoptosis; chromosome conformation capture; genome architecture; long-distance gene regulation; p53