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| Title | Polymerization of ZBTB transcription factors regulates chromatin occupancy. |
|---|---|
| Journal, issue, pages | Mol Cell, Vol. 84, Issue 13, Page 2511-22524.e8, Year 2024 |
| Publish date | Jul 11, 2024 |
Authors | Paul M C Park / Jiho Park / Jared Brown / Moritz Hunkeler / Shourya S Roy Burman / Katherine A Donovan / Hojong Yoon / Radosław P Nowak / Mikołaj Słabicki / Benjamin L Ebert / Eric S Fischer / ![]() |
| PubMed Abstract | BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, ...BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression. |
External links | Mol Cell / PubMed:38996460 / PubMed Central |
| Methods | EM (single particle) / EM (helical sym.) |
| Resolution | 3.7 - 8.1 Å |
| Structure data | EMDB-44389, PDB-9b9r: EMDB-44391, PDB-9b9v: |
| Source |
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Keywords | TRANSCRIPTION / BTB domain / transcription factor / ZBTB protein |
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homo sapiens (human)
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