8PK5

INTS13-INTS14 complex with ZNF609

Summary for 8PK5

• Entry DOI: 10.2210/pdb8pk5/pdb
• Descriptor: Integrator complex subunit 13, Integrator complex subunit 14,Zinc finger protein 609, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: protein complex, rna binding, structural protein, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 141223.56

Authors

Sabath, K.,Jonas, S. (deposition date: 2023-06-25, release date: 2024-07-03, Last modification date: 2024-11-06)

Primary citation

Sabath, K.,Nabih, A.,Arnold, C.,Moussa, R.,Domjan, D.,Zaugg, J.B.,Jonas, S.
Basis of gene-specific transcription regulation by the Integrator complex.
Mol.Cell, 84:2525-, 2024

PubMed Abstract: The 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.

PubMed: 38906142
DOI: 10.1016/j.molcel.2024.05.027

Experimental method

X-RAY DIFFRACTION (2.5 Å)