BACH Transcription Factors in Innate and Adaptive Immunity

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2017 May 3

PMID 28461702

Citations 51

Authors

Kazuhiko Igarashi

Tomohiro Kurosaki

Rahul Roychoudhuri

Affiliations

Soon will be listed here.

Abstract

BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4 regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions. The findings contribute to a general understanding of how transcriptional repressors shape lineage commitment and cell-type-specific functions through repression of alternative lineage programmes.

Citing Articles

Raman spectroscopy and bioinformatics-based identification of key genes and pathways capable of distinguishing between diffuse large B cell lymphoma and chronic lymphocytic leukemia.

Liang H, Cao Z, Ren Y, Li Y, Wang H, Sun F Front Immunol. 2025; 16:1516946.

PMID: 40070829 PMC: 11893875. DOI: 10.3389/fimmu.2025.1516946.

The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.

Mancuso C Antioxidants (Basel). 2025; 14(2).

PMID: 40002374 PMC: 11852105. DOI: 10.3390/antiox14020187.

METTL3 mediates CPB1 expression by regulating transcription factor BACH2 to promote apoptosis and oxidative stress of lens epithelial cells.

Sheng Z, Pan Y, Shao L, Bao Y J Bioenerg Biomembr. 2025; .

PMID: 39982642 DOI: 10.1007/s10863-025-10054-1.

The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.

Wei X, He Y, Yu Y, Tang S, Liu R, Guo J Adv Sci (Weinh). 2025; 12(10):e2412850.

PMID: 39887888 PMC: 11905017. DOI: 10.1002/advs.202412850.

Cancer vaccine designed from homologous ferritin-based fusion protein with enhanced DC-T cell crosstalk for durable adaptive immunity against tumors.

Wu J, Liang J, Li S, Lu J, Li Y, Zhang B Bioact Mater. 2025; 46:516-530.

PMID: 39868073 PMC: 11764028. DOI: 10.1016/j.bioactmat.2024.12.029.

References

Zhang D, Glass C . Towards an understanding of cell-specific functions of signal-dependent transcription factors. J Mol Endocrinol. 2013; 51(3):T37-50. PMC: 4128342. DOI: 10.1530/JME-13-0216. View

Scholtysik R, Kreuz M, Hummel M, Rosolowski M, Szczepanowski M, Klapper W . Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis. Int J Cancer. 2014; 136(5):1033-42. DOI: 10.1002/ijc.29072. View

Opferman J, Letai A, Beard C, Sorcinelli M, Ong C, Korsmeyer S . Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003; 426(6967):671-6. DOI: 10.1038/nature02067. View

Ota K, Brydun A, Itoh-Nakadai A, Sun J, Igarashi K . Bach1 deficiency and accompanying overexpression of heme oxygenase-1 do not influence aging or tumorigenesis in mice. Oxid Med Cell Longev. 2014; 2014:757901. PMC: 4094857. DOI: 10.1155/2014/757901. View

Alam J, Killeen E, Gong P, Naquin R, Hu B, Stewart D . Heme activates the heme oxygenase-1 gene in renal epithelial cells by stabilizing Nrf2. Am J Physiol Renal Physiol. 2002; 284(4):F743-52. DOI: 10.1152/ajprenal.00376.2002. View

Hira S, Tomita T, Matsui T, Igarashi K, Ikeda-Saito M . Bach1, a heme-dependent transcription factor, reveals presence of multiple heme binding sites with distinct coordination structure. IUBMB Life. 2007; 59(8-9):542-51. DOI: 10.1080/15216540701225941. View

Brand M, Ranish J, Kummer N, Hamilton J, Igarashi K, Francastel C . Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics. Nat Struct Mol Biol. 2004; 11(1):73-80. DOI: 10.1038/nsmb713. View

Haldar M, Kohyama M, So A, Kc W, Wu X, Briseno C . Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell. 2014; 156(6):1223-1234. PMC: 4010949. DOI: 10.1016/j.cell.2014.01.069. View

van der Weyden L, Arends M, Campbell A, Bald T, Wardle-Jones H, Griggs N . Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. Nature. 2017; 541(7636):233-236. PMC: 5603286. DOI: 10.1038/nature20792. View

10.

Sawcer S, Hellenthal G, Pirinen M, Spencer C, Patsopoulos N, Moutsianas L . Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011; 476(7359):214-9. PMC: 3182531. DOI: 10.1038/nature10251. View

11.

Martinez F, Gordon S . The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014; 6:13. PMC: 3944738. DOI: 10.12703/P6-13. View

12.

Shinnakasu R, Inoue T, Kometani K, Moriyama S, Adachi Y, Nakayama M . Regulated selection of germinal-center cells into the memory B cell compartment. Nat Immunol. 2016; 17(7):861-9. DOI: 10.1038/ni.3460. View

13.

Watanabe-Matsui M, Muto A, Matsui T, Itoh-Nakadai A, Nakajima O, Murayama K . Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2. Blood. 2011; 117(20):5438-48. DOI: 10.1182/blood-2010-07-296483. View

14.

Glover J, Harrison S . Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature. 1995; 373(6511):257-61. DOI: 10.1038/373257a0. View

15.

Nakamura A, Ebina-Shibuya R, Itoh-Nakadai A, Muto A, Shima H, Saigusa D . Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function. J Exp Med. 2013; 210(11):2191-204. PMC: 3804940. DOI: 10.1084/jem.20130028. View

16.

Cooper J, Smyth D, Smiles A, Plagnol V, Walker N, Allen J . Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet. 2008; 40(12):1399-401. PMC: 2635556. DOI: 10.1038/ng.249. View

17.

Kometani K, Nakagawa R, Shinnakasu R, Kaji T, Rybouchkin A, Moriyama S . Repression of the transcription factor Bach2 contributes to predisposition of IgG1 memory B cells toward plasma cell differentiation. Immunity. 2013; 39(1):136-47. DOI: 10.1016/j.immuni.2013.06.011. View

18.

Oyake T, Itoh K, Motohashi H, Hayashi N, Hoshino H, Nishizawa M . Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site. Mol Cell Biol. 1996; 16(11):6083-95. PMC: 231611. DOI: 10.1128/MCB.16.11.6083. View

19.

Tan M, Lim H, Bennett E, Shi Y, Harper J . Parallel SCF adaptor capture proteomics reveals a role for SCFFBXL17 in NRF2 activation via BACH1 repressor turnover. Mol Cell. 2013; 52(1):9-24. PMC: 3981468. DOI: 10.1016/j.molcel.2013.08.018. View

20.

Lee G, Fields P, Griffin T, Flavell R . Regulation of the Th2 cytokine locus by a locus control region. Immunity. 2003; 19(1):145-53. DOI: 10.1016/s1074-7613(03)00179-1. View