BACH1

What is BACH1 protein?

BACH1 gene (BTB domain and CNC homolog 1) is a protein coding gene which situated on the long arm of chromosome 21 at locus 21q21. This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. The BACH1 protein is consisted of 736 amino acids and BACH1 molecular weight is approximately 82.0 kDa.

What is the function of BACH1 protein?

BACH1 protein is a transcription factor widely expressed in a variety of mammalian tissues. It works primarily by heterodimerizing with small Maf proteins and binding to Maf recognition elements on target gene promoters, typically acting as a transcriptional suppressor. BACH1 plays a key regulatory role in various biological processes such as oxidative stress response, cell cycle control, heme homeostasis, inflammation and immune response. Under oxidative stress, BACH1 can inhibit the expression of antioxidant genes, such as heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In addition, BACH1 is also involved in genes related to the regulation of cell cycle and apoptosis pathways, which influence the occurrence of neurodegenerative diseases and virus-induced cancers. The abnormal function of BACH1 is closely related to cardiovascular diseases, the maintenance of stem cell pluripotency, and the development of tumors.

BACH1 related signaling pathway

Bach1-related signaling pathways are mainly involved in oxidative stress response and heme metabolism. BACH1 is a transcriptional suppressor that senses oxidative stress by binding to heme and regulates the expression of antioxidant genes. Under oxidative stress, the binding of BACH1 to DNA is weakened, resulting in the release of the inhibition of genes driven by the anti-oxidative response element (ARE), such as heme oxygenase 1 and thioredoxin, thus promoting the expression of these genes and enhancing the antioxidant capacity of cells. In addition, BACH1 is involved in regulating the differentiation and function of immune cells, especially in T cells, affecting inflammation and the development of autoimmune diseases.

BACH1 related diseases

The abnormal function of BACH1 has been associated with a variety of diseases, especially its role in cardiovascular diseases, stem cell pluripotency maintenance and tumor progression. For example, BACH1 is involved in the occurrence and development of ischemic angiogenesis, hypertension, atherosclerosis and other cardiovascular diseases. In tumors, BACH1 promotes tumor proliferation and metastasis by reprogramming tumor metabolism and altering epithel-mesenchymal transformation phenotype, while it may inhibit tumor growth by regulating iron death, showing a dual role in tumors. In addition, BACH1 is also associated with insulin resistance, and its expression is up-regulated in the liver of patients with metabolic disorders and non-alcoholic fatty liver. Targeted inhibition of liver BACH1 can improve the liver insulin sensitivity of mice fed high fat diet and db/db diabetic mice, providing a new target for the treatment of type 2 diabetes and related metabolic diseases.

Fig1. BACH1 downstream targets in various types of cancers. (Abirami Arunachalam, 2021)

Bioapplications of BACH1

The biological application of BACH1 mainly focuses on the study and regulation of oxidative stress response, heme metabolism and immune cell function. As a transcription factor, rhBACH1 can be used in experimental studies to simulate or modulate gene expression under oxidative stress, helping to reveal antioxidant defense mechanisms and pathways associated with heme catabolism. In addition, rhBACH1 has applications in immunological research, where it may be used to explore the differentiation and functional regulation of T cells, as well as pathological processes in autoimmune diseases. The potential therapeutic effects of rhBACH1 can be evaluated in vitro or in animal models, especially in diseases involving oxidative damage and abnormal immune responses. However, the clinical application of rhBACH1 still requires further research to ensure its safety and efficacy.

Case Study 1: Ting Wang, 2023

This study shows that BACH1, a redox-sensitive transcription factor, significantly influences lung cancer angiogenesis beyond the role of HIFs. Its expression increases under low ROS levels and hypoxia, promoting angiogenesis gene expression. Antioxidants enhance BACH1's effects, and it makes tumors more susceptible to antiangiogenic treatment. BACH1 activity correlates with angiogenesis in lung cancer patient samples, highlighting its role as a key regulator of tumor angiogenesis.

Fig1. BACH1 protein levels in spheroids.

Fig2. Comparisons of VEGFA and VEGFR2 expression with BACH1 protein expression in human NSCLC tumor sections.

Case Study 2: C Liu, 2022

This study explored how BACH1 affects human dental pulp stem cells' (hDPSCs) growth and ability to differentiate into odontoblasts, which is crucial for dental pulp regeneration. BACH1 is more expressed in odontoblasts. Its levels first decrease then increase during hDPSC odontoblastic differentiation. Reducing BACH1 slowed cell growth, affected cell cycle progression, and reduced odontoblastic differentiation markers. Conversely, increasing BACH1 boosted cell proliferation and differentiation. These findings suggest BACH1 is important for hDPSC function and could be useful for clinical applications in dental pulp regeneration.

Fig3. Changes in the total protein level of BACH1, DMP1 and DSPP on OM.

Fig4. mRNA level of BACH1, HMOX-1 and odontogenic markers in LV-NC and LV-shBACH1 hDPSCs.

BACH1 has several biochemical functions, for example, RNA polymerase II distal enhancer sequence-specific DNA binding,heme binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by BACH1 itself. We selected most functions BACH1 had, and list some proteins which have the same functions with BACH1. You can find most of the proteins on our site.

BACH1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with BACH1 here. Most of them are supplied by our site. Hope this information will be useful for your research of BACH1.

MAFG;MAF;FOS;ATF2;CREB1;ATF7;ATF1;DDIT3;BATF;meq_gahvm;MAFB;Bach1;ANAPC5;h0y2u5_human;TMEM208