3wts
Crystal structure of the complex comprised of ETS1, RUNX1, CBFBETA, and the tcralpha gene enhancer DNACrystal structure of the complex comprised of ETS1, RUNX1, CBFBETA, and the tcralpha gene enhancer DNA
Structural highlights
FunctionPEBB_MOUSE CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBFB enhances DNA binding by RUNX1. Publication Abstract from PubMedCooperative assemblies of transcription factors (TFs) on target gene enhancers coordinate cell proliferation, fate specification, and differentiation through precise and complicated transcriptional mechanisms. Chemical modifications, such as phosphorylation, of TFs induced by cell signaling, further modulate the dynamic cooperativity of TFs. In this study, we found that various Ets1-containing TF-DNA complexes respond differently to calcium-induced phosphorylation of Ets1, which is known to inhibit Ets1-DNA binding. Crystallographic analysis of a complex comprising Ets1, Runx1, and CBFbeta at the TCRalpha enhancer, revealed that Ets1 acquires robust binding stability in the Runx1 and DNA-complexed state, via allosteric mechanisms. This allows phosphorylated Ets1 to be retained at the TCRalpha enhancer with Runx1, in contrast to other Ets1 target gene enhancers including mb-1 and stromelysin-1. This study provides a structure-based model for cell signaling-dependent regulation of target genes, mediated via chemical modification of TFs. A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions.,Shiina M, Hamada K, Inoue-Bungo T, Shimamura M, Uchiyama A, Baba S, Sato K, Yamamoto M, Ogata K J Mol Biol. 2014 Jul 29. pii: S0022-2836(14)00368-4. doi:, 10.1016/j.jmb.2014.07.020. PMID:25083921[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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