8pk5
INTS13-INTS14 complex with ZNF609
Structural highlights
FunctionINT13_HUMAN Crucial regulator of the mitotic cell cycle and development. At prophase, required for dynein anchoring to the nuclear envelope important for proper centrosome-nucleus coupling. At G2/M phase, may be required for proper spindle formation and execution of cytokinesis. Probable component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing (PubMed:23904267).[1] [2] [3] [4] [5] Publication Abstract from PubMedThe Integrator complex attenuates gene expression via the premature termination of RNA polymerase II (RNAP2) at promoter-proximal pausing sites. It is required for stimulus response, cell differentiation, and neurodevelopment, but how gene-specific and adaptive regulation by Integrator is achieved remains unclear. Here, we identify two sites on human Integrator subunits 13/14 that serve as binding hubs for sequence-specific transcription factors (TFs) and other transcription effector complexes. When Integrator is attached to paused RNAP2, these hubs are positioned upstream of the transcription bubble, consistent with simultaneous TF-promoter tethering. The TFs co-localize with Integrator genome-wide, increase Integrator abundance on target genes, and co-regulate responsive transcriptional programs. For instance, sensory cilia formation induced by glucose starvation depends on Integrator-TF contacts. Our data suggest TF-mediated promoter recruitment of Integrator as a widespread mechanism for targeted transcription regulation. Basis of gene-specific transcription regulation by the Integrator complex.,Sabath K, Nabih A, Arnold C, Moussa R, Domjan D, Zaugg JB, Jonas S Mol Cell. 2024 Jun 17:S1097-2765(24)00474-X. doi: 10.1016/j.molcel.2024.05.027. PMID:38906142[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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