Disease relevance of BACH1

• Overexpression of transcription factor BACH1 in fetal Down syndrome brain [1].
• BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ [2].
• We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1 [3].
• HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells [4].
• BACH1 517C-->T transition impairs protein translocation to nucleus: a role in breast cancer susceptibility [5]?

Psychiatry related information on BACH1

• Aberrant protein expression of transcription factors BACH1 and ERG, both encoded on chromosome 21, in brains of patients with Down syndrome and Alzheimer's disease [6].

High impact information on BACH1

• Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21 [7].
• We have investigated the DNA substrate specificity of BACH1 (BRCA1-associated C-terminal helicase) [8].
• Using small interfering RNAs targeted to human Bach-1 mRNA, we investigated whether modulation of human hepatic Bach-1 expression by small interfering (si)RNA technology influences heme oxygenase-1 gene expression [9].
• Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells [3].
• Therefore, Bach1 functions as a hypoxia-inducible repressor for the HO-1 gene, thereby contributing to fine-tuning of oxygen homeostasis in human cells [3].

Chemical compound and disease context of BACH1

• To investigate the involvement of Bach1 in the heme-dependent regulation of the expression of the alpha-globin gene, human erythroleukemia K562 cells were cultured with succinylacetone (SA), a heme biosynthetic inhibitor, and the level of alpha-globin mRNA was examined [10].

Biological context of BACH1

• We then isolated the full-length coding region of the human BACH1 gene using expressed sequence tags, reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends [11].
• The BACH1 gene maps in a relatively gene-poor region on 21q22.1 in yeast artificial chromosome 814c1 of the collection of Chumakov et al [11].
• Isolation of the human BACH1 transcription regulator gene, which maps to chromosome 21q22.1 [11].
• The contribution of the BACH1 gene to the pathophysiology of trisomy or monosomy 21 is unknown [11].
• Increased BACH1, however, did not lead to decreased HO1, which would have explained oxidative stress observed in fetal DS [1].

Anatomical context of BACH1

• These and other results suggest a key role of down-regulation of Bach1 and up-regulation of HO-1 in diminishing cytotoxic effects of HCV proteins in human hepatocytes [4].
• Heme-dependent up-regulation of the alpha-globin gene expression by transcriptional repressor Bach1 in erythroid cells [10].
• Expression levels of HO-1 mRNA were reduced by interferon-gamma in two human RPE cell lines, D407 and ARPE-19, which was consistently associated with the induction of mRNA for Bach1, a transcriptional repressor for the HO-1 gene [12].
• Both immortalized rat fibroblasts (RAT-1) and human lung cancer cells (Mv1Lu) exposed to TAR (25 microg/ml), exhibited an initial (6 h) induction of HO-1, followed by a late (24 h) repression due to the activation of Bach1 [13].
• This interaction occurs via endothelial cell receptor VE-cadherin and fibrin beta chain 15-42 regions [Bach, T. L., et al. (1998) J. Biol. Chem. 272, 30719-30728] [14].

Associations of BACH1 with chemical compounds

• Expression of HO-1 was also reduced in human cells when exposed to interferon-gamma or an iron chelator desferrioxamine, each of which induced Bach1 expression [3].
• Sodium arsenite, a strong inducer of oxidative stress and HO-1, reduced Bach1 expression in wild type Huh-7 cells, and NAC partially abrogated this decrease [4].
• Substitution of the conserved cysteine residue in the DNA binding domain of Bach1 to serine (C574S mutant) caused a refractory response to the diamide-mediated reactivation of the Bach1-suppressed reporter activity [15].
• The NA site-binding activity of Bach1 in K562 increased upon SA-treatment, and the increase was diminished by the addition of hemin [10].
• This article reports the first evidence that beta-carotene, combined with cigarette smoke condensate (TAR), regulates heme oxygenase-1 (HO-1) via its transcriptional factor Bach1 and modulates cell growth [13].

Regulatory relationships of BACH1

• More specifically, BACH1 suppresses expression of HO1 [1].
• Diamide showed restricted Nrf2 nuclear translocation and ARE-driven reporter activity but reversed the ARE transcriptional activity suppressed by ectopically expressed Bach1 [15].

Other interactions of BACH1

• Immunoblotting was used to determine protein levels of TF BACH1, ERG, SIM2 and RUNX1 [6].
• Several signaling molecules (e.g., mitogen-activated protein kinases), transcriptional regulators (activator protein-1, NF-E2-related factor-2, hypoxia-inducible factor-1, Bach-1), as well as two enhancer regions in the ho-1 5' regulatory region, participate in the regulation of the ho-1 gene [16].
• Other recent work has implicated Bach1, a heme binding protein that represses gene expression, in the regulation of HO-1 gene expression [4].
• Two tandem BRCA1 C-terminal (BRCT) domains are essential for the tumor suppression activity of BRCA1 and interact in a phosphorylation-dependent manner with proteins involved in DNA damage-induced checkpoint control, including the DNA helicase BACH1 and the CtBP-interacting protein (CtIP) [17].
• Three genes, BACH1, TP53BPL, and H2B/S, were consistently expressed as a significant cluster associated with the low-risk ALL subgroups [18].
• The loss of BACH1 function in human keratinocytes results almost exclusively in HMOX1 induction, suggesting that BACH1 may function as a rheostat regulating levels of intracellular free heme [19].

Analytical, diagnostic and therapeutic context of BACH1

• Brain homogenates were subject to immunoblotting using goat-anti-BACH1, rabbit anti-heme oxygenase 1 (HO1), rabbit anti-ERG, rabbit anti-RUNX1 and goat anti-SIM2 l [1].
• Several hydrogen bonds and salt bridges that stabilize the BRCA1-BACH1 complex are missing in the BRCA1-CtIP interaction, offering a structural basis for the approximately 5-fold lower affinity of BRCA1 for CtIP compared to that of BACH1, as determined by isothermal titration calorimetry [17].
• The association of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: results from the BACH survey [20].
• Cohort and case-control studies were performed on all adult and pediatric AES patients admitted to the Neurology Service of Bach Mai Hospital between June 5 and August 3, 1995 [21].
• Bach recently surveyed 273 MDA clinic directors and co-directors from 167 clinics, to evaluate their current use of mechanical ventilation [22].

References