| Autor: |
Platt, James L, Salama, Rafik, Smythies, James, Choudhry, Hani, Davies, James OJ, Hughes, Jim R, Ratcliffe, Peter J, Mole, David R |
| Zdroj: |
EMBO Reports; Oct2016, Vol. 17 Issue 10, p1410-1421, 12p |
| Abstrakt: |
Hypoxia-inducible factor ( HIF) directs an extensive transcriptional cascade that transduces numerous adaptive responses to hypoxia. Pan-genomic analyses, using chromatin immunoprecipitation and transcript profiling, have revealed large numbers of HIF-binding sites that are generally associated with hypoxia-inducible transcripts, even over long chromosomal distances. However, these studies do not define the specific targets of HIF-binding sites and do not reveal how induction of HIF affects chromatin conformation over distantly connected functional elements. To address these questions, we deployed a recently developed chromosome conformation assay that enables simultaneous high-resolution analyses from multiple viewpoints. These assays defined specific long-range interactions between intergenic HIF-binding regions and one or more promoters of hypoxia-inducible genes, revealing the existence of multiple enhancer-promoter, promoter-enhancer, and enhancer-enhancer interactions. However, neither short-term activation of HIF by hypoxia, nor long-term stabilization of HIF in von Hippel-Lindau ( VHL)-defective cells greatly alters these interactions, indicating that at least under these conditions, HIF can operate on preexisting patterns of chromatin-chromatin interactions that define potential transcriptional targets and permit rapid gene activation by hypoxic stress. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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