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FLASH GENE
Symbol BACH1 contributors: mct - updated : 03-10-2016
HGNC name BTB and CNC homology 1, basic leucine zipper transcription factor 1
HGNC id 935
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal BTB (broad complex-tamtrack-bric-a-brac) domain, that is thought to contribute to DNA binding through oligomerization with neighboring BACH1 heterodimers to stabilize their interactions with DNA
  • POZ (pox virus and zinc finger) protein interaction domain
  • a C terminal basic leucine zipper (bZIP) of the cap'n'collar type, and is also excluded from mitotic chromatin by a C-terminal cytoplasmic localization sequence dependent and leptomycin B sensitive process
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Bac-1 transcription factor
    Homologene
    FAMILY
  • DEAH helicase family
  • bZIP family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • predominantly localized to the nucleus of control cells
  • despite its role in transcription, is predominantly exported to the cytoplasm in a XPO1-dependent manner
    • basic FUNCTION
  • activator in cultured erythroid cells
  • transcription repressor in fibroblasts
  • hematopoietic transcription factor implicated in megakaryocytes differentiation
  • having a specific and selective ability to repress expression of hepatic HMOX1
  • heme-regulated repressor of alpha-globin genes, playing a role in redox induction of HMOX1 and NQO1, though the exact mechanism of this repression is not clear
  • confers an additional level of regulation to ARE-dependent genes that reveals a new dimension to the oxidative stress response
  • may serve to not only facilitate DNA repair, but also maintain BRCA1 in DNA damage foci
  • may function as a rheostat regulating levels of intracellular free heme
  • acts as a relatively specific transcription factor, as judged by the small number of target regions compared with other bZIP transcription factors for which up to several thousands of peaks have been observed
  • plays a specific role in sensing and regulating HMOX-dependent heme turnover and maintains intracellular heme homeostasis by functioning as a fulcrum that balances intracellular heme levels with cellular redox status through the expression of HMOX1
  • repressor of the oxidative stress response
  • inhibits oxidative stress-inducible genes, and is a crucial negative regulator of oxidative stress–induced cellular senescence
  • connects oxygen metabolism and cellular senescence as a negative regulator of TP53
  • TOPBP1 and BACH1 are required for ATR-dependent phosphorylation events in response to replication stress
  • plays a critical role in regulating HMOX1 gene expression in acute myeloid leukemia cells and its expression suppresses their
    • survival by downregulating HMOX1 expression
  • in response to oxidative stress, regulates the oxidation state through the negative control of heme oxygenase-1 expression prior to terminal keratinocyte differentiation
  • its function may affect not only the pathogenesis of skin diseases but also the process of skin aging
  • heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels
  • is a repressor of the oxidative stress response, and a negative regulator of ROS-induced cellular senescence directed by TP53
  • is the master regulator of breast cancer bone metastasis
  • heme may regulate BACH1 as an extracellular signaling molecule
  • BACH2 functions with BACH1 and EBF1 to promote B cell development by repressing myeloid genes in common lymphoid progenitor (CLP) (
  • regulates genes involved in the oxidative stress response and cell-cycle progression
  • suppresses cell proliferation and induces cell-cycle arrest and apoptosis by increasing mitochondrial ROS production
  • acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative
  • BACH1 and BACH2 work in a complementary manner to maintain the normal function of the alveolar macrophages (AMs) and surfactant homeostasis in the lung
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer with MAFK
  • forms a heterodimer with the small Maf oncoproteins and binds to the Maf-recognition element (MARE) to inhibit target genes, including HMOX1
  • bound to the ARE enhancer motifs preventing NFE2L2 from binding and thereby repressing transcription
  • complex with TP53 on a subset of its target genes to restrain the transcriptional activity of TP53 by recruiting histone deacetylase 1 (HDAC1), thus inhibiting the process of cellular senescence
  • novel role of BACH1 in the regulation of mitotic chromosome dynamics
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding NF-E2 binding sites with MAFK coordinating transcription activation and repression by MAFK
  • binding directly to BRCT repeats of BRCA1 and contributing to its activity
  • interacting with NFE2L2, bound to the ARE enhancer motifs preventing NFE2L2 from binding and thereby
  • binds HMOX1 antioxidant response elements and represses transcription
  • repressing transcription (dynamic roles of BACH1 and NFE2L2 in the transcription of the heme oxygenase-1 (HMOX1) gene)
  • interacts directly with the BRCA1 C-terminal BRCT repeats, which are important for BRCA1 DNA repair
  • increased expression of the BACH1 target sequestosome 1 (SQSTM1), a multifunctional ubiquitin-binding protein that serves as a storage place for ubiquitinated protein
  • specific interaction between TOPBP1 and BACH1/FANCJ, a DNA helicase involved in the repair of DNA crosslinks
  • key player in the physiological regulation of oxidative stress, where it acts as a repressor of its main target, HMOX1
  • PSAP and MAPT are direct BACH1 target genes, both of which have been identified as potential biomarkers for the detection of Alzheimer disease
  • the CDKN2A-BACH1 interaction constitutes a regulatory pathway of TP53 in parallel with the CDKN2A-MDM2 pathway
  • critical role of BACH1 in cell transformation and tumor growth induced by activated HRAS
  • TGFB1 induced expression of transcription factors MAFK and BACH1
  • suppresses angiogenesis after ischemic injury and impairs Wnt/CTNNB1 signaling by disrupting the interaction between CTNNB1 and TCF4
  • transcriptional repressor of Heme oxygenase-1 (HO-1), which is cytoprotective through its antioxidant effects
  • HOXB8 interacted with a key metastasis regulator BACH1 and instigated BACH1-mediated transcriptional cascade by directly occupying and activating BACH1 gene transcription together with BACH1 itself
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in acute megakaryoblastic leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    promising treatment target for the treatment of vascular diseases
    cancerhemopathy 
    functional upregulation of BACH1 is a potential strategy for antileukemic therapy
    immunologyautoimmunearticular
    inactivation of BACH11 is a novel target and signaling pathway in OA prevention
    ANIMAL & CELL MODELS