BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction between BAF and divergent binding partners has remained unclear. Here, we tested the hypothesis that scaffold proteins augment BAF's binding repertoire by examining β-catenin (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast to exclusively IDR-driven mechanisms, adapter function is mediated by direct association of ARID1A with β-catenin's folded Armadillo repeats. β-catenin similarly linked cBAF to YAP1, SOX2, FOXO3, and CBP/p300, reflecting a general IDR-mediated mechanism for modular coordination between factors. Molecular visualization highlights β-catenin's adapter role for interaction of cBAF with binding partners.

• Klíčová slova
• IDRs, adrenocortical carcinoma, chromatin remodeling, co-activators, scaffold proteins, steroid hormones, transcription factors, transcription regulators, unstructured protein,
• MeSH
• adaptorové proteiny signální transdukční metabolismus   genetika   MeSH
• beta-katenin * metabolismus   genetika   chemie   MeSH
• DNA vazebné proteiny * metabolismus   genetika   chemie   MeSH
• fosfoproteiny metabolismus   genetika   MeSH
• HEK293 buňky MeSH
• jaderné proteiny * metabolismus   genetika   MeSH
• lidé MeSH
• protein FOXO3 metabolismus   genetika   MeSH
• signální proteiny YAP MeSH
• signální transdukce MeSH
• steroidogenní faktor 1 * metabolismus   genetika   MeSH
• transkripční faktory p300-CBP metabolismus   genetika   MeSH
• transkripční faktory * metabolismus   genetika   chemie   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vnitřně neuspořádané proteiny * metabolismus   genetika   MeSH
• zesilovače transkripce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• ARID1A protein, human MeSH Prohlížeč
• beta-katenin * MeSH
• CTNNB1 protein, human MeSH Prohlížeč
• DNA vazebné proteiny * MeSH
• fosfoproteiny MeSH
• jaderné proteiny * MeSH
• NR5A1 protein, human MeSH Prohlížeč
• protein FOXO3 MeSH
• signální proteiny YAP MeSH
• steroidogenní faktor 1 * MeSH
• transkripční faktory p300-CBP MeSH
• transkripční faktory * MeSH
• vnitřně neuspořádané proteiny * MeSH
• YAP1 protein, human MeSH Prohlížeč

Eukaryotic transcription is dependent on specific histone modifications. Their recognition by chromatin readers triggers complex processes relying on the coordinated association of transcription regulatory factors. Although various modification states of a particular histone residue often lead to differential outcomes, it is not entirely clear how they are discriminated. Moreover, the contribution of intrinsically disordered regions outside of the specialized reader domains to nucleosome binding remains unexplored. Here, we report the structures of a PWWP domain from transcriptional coactivator LEDGF in complex with the H3K36 di- and trimethylated nucleosome, indicating that both methylation marks are recognized by PWWP in a highly conserved manner. We identify a unique secondary interaction site for the PWWP domain at the interface between the acidic patch and nucleosomal DNA that might contribute to an H3K36-methylation independent role of LEDGF. We reveal DNA interacting motifs in the intrinsically disordered region of LEDGF that discriminate between the intra- or extranucleosomal DNA but remain dynamic in the context of dinucleosomes. The interplay between the LEDGF H3K36-methylation reader and protein binding module mediated by multivalent interactions of the intrinsically disordered linker with chromatin might help direct the elongation machinery to the vicinity of RNA polymerase II, thereby facilitating productive elongation.

• Publikační typ
• časopisecké články MeSH