bHLHLZ

bHLHLZ is a term used to describe transcription factors that contain a basic region followed by a helix-loop-helix leucine zipper architecture. In more standard terminology, such proteins are classified as bHLH-LZ transcription factors. The term is sometimes encountered in databases or older literature as bHLHLZ to emphasize the combination of the basic region, the HLH dimerization module, and the leucine zipper.

These proteins typically have a short, highly basic region responsible for DNA contact, followed by a helix-loop-helix domain that mediates dimerization, and a leucine zipper motif that stabilizes homodimeric or heterodimeric complexes. The dimer binds to E-box sequences (CANNTG) in target gene promoters, regulating transcription.

Well-characterized members include c-Myc and its partner MAX, which form heterodimers to activate a broad transcription program, and related factors such as USF family members, which also use the bHLH-LZ architecture. The combination of DNA binding by the basic region and dimerization via the HLH/LZ modules allows combinatorial control of gene expression and the formation of diverse transcriptional complexes.

Biological roles of bHLH-LZ factors include control of cell proliferation, differentiation, and metabolic regulation. Because their activity can drive cell growth, misregulation is linked to developmental disorders and cancer. Research on bHLH-LZ proteins continues to emphasize their dimerization partners, DNA binding specificity, and context-dependent transcriptional outcomes.