Cooperation between bHLH transcription factors and histones for DNA access

The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members1. Here we investigate how chromatinized are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX circadian factor CLOCK-BMAL1 (refs. 2,3). Both bind to preferentially near nucleosomal entry-exit sites. Structural studies with engineered or native nucleosome sequences show that triggers release from histones gain access. Atop H2A-H2B acidic patch4, Per-Arnt-Sim (PAS) dimerization domains engage histone octamer disc. Binding tandem E-boxes5-7 at endogenous occurs through direct interactions between protomers is important for cycling. At internal E-boxes, leucine zipper can also interact H2B H3, its binding indirectly enhanced OCT4 elsewhere on nucleosome. E-box position type domain jointly determine contact, affinity degree competition cooperativity other nucleosome-bound factors.