6kn5

Crystal structure of AFF4 C-terminal domain

spinqualitylabelsall models 6kn5, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed As approximately 70% of human breast tumors are estrogen receptor alpha (ERalpha)-positive, estrogen and ERalpha play essential roles in breast cancer development. By interrupting the ERalpha signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERalpha) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting breast cancer cell growth. More importantly, a AFF4 mutant which lacks H3K27ac interaction failed to rescue ESR1 gene expression, suggesting H3K27 acetylation at TSS region is a key mark bridging the transition from transcriptional initiation to elongation, and perturbing SEC function can be an alternative strategy for targeting ERalpha signaling pathway at chromatin level. Acetylation of histone H3K27 signals the transcriptional elongation for estrogen receptor alpha.,Gao Y, Chen L, Han Y, Wu F, Yang WS, Zhang Z, Huo T, Zhu Y, Yu C, Kim H, Lee M, Tang Z, Phillips K, He B, Jung SY, Song Y, Zhu B, Xu RM, Feng Q Commun Biol. 2020 Apr 7;3(1):165. doi: 10.1038/s42003-020-0898-0. PMID:32265480 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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