| First Author | Michael AK | Year | 2023 |
| Journal | Nature | Volume | 619 |
| Issue | 7969 | Pages | 385-393 |
| PubMed ID | 37407816 | Mgi Jnum | J:340494 |
| Mgi Id | MGI:7525799 | Doi | 10.1038/s41586-023-06282-3 |
| Citation | Michael AK, et al. (2023) Cooperation between bHLH transcription factors and histones for DNA access. Nature 619(7969):385-393 |
| abstractText | The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members(1). Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX and the circadian transcription factor CLOCK-BMAL1 (refs. (2,3)). Both transcription factors bind to E-boxes preferentially near the nucleosomal entry-exit sites. Structural studies with engineered or native nucleosome sequences show that MYC-MAX or CLOCK-BMAL1 triggers the release of DNA from histones to gain access. Atop the H2A-H2B acidic patch(4), the CLOCK-BMAL1 Per-Arnt-Sim (PAS) dimerization domains engage the histone octamer disc. Binding of tandem E-boxes(5-7) at endogenous DNA sequences occurs through direct interactions between two CLOCK-BMAL1 protomers and histones and is important for circadian cycling. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B and H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerization domain jointly determine the histone contact, the affinity and the degree of competition and cooperativity with other nucleosome-bound factors. |
