Bach1

Bach1, or BTB and CNC homology 1, is a transcription factor in mammals belonging to the CNC-bZIP family. It is encoded by the BACH1 gene and functions as a repressor of oxidative stress response genes under basal conditions. The protein contains an N-terminal BTB/POZ domain and a C-terminal CNC-bZIP DNA-binding domain, and it forms heterodimers with small Maf proteins such as MAFF and MAFG to recognize Maf recognition elements (MARE) in target gene promoters.

BACH1 primarily acts to suppress expression of antioxidant and cytoprotective genes, including heme oxygenase-1 (HMOX1) and other ARE-containing genes. Its activity is opposed by NRF2, a transcription factor that activates ARE-driven genes. Regulation of BACH1 is tightly linked to cellular redox state and heme levels: in response to oxidative stress or high heme, BACH1 is exported from the nucleus and targeted for proteasomal degradation, allowing NRF2 to accumulate in the nucleus and induce transcription of protective genes.

Beyond redox control, BACH1 participates in iron and heme homeostasis and can influence inflammatory responses. Its role in cancer biology has been explored, with evidence that BACH1 activity can affect tumor progression and metastasis in a context-dependent manner, potentially through modulation of oxidative stress and metabolic pathways.

Clinically, BACH1 is studied as a regulator of cytoprotective gene expression, and approaches that reduce BACH1 activity or promote its degradation are being considered to enhance antioxidant defenses in diseases characterized by oxidative stress.