BACH2

Transcription regulator protein BACH2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) is a protein that in humans is encoded by the BACH2 gene.[5][6][7] It contains a BTB/POZ domain at its N-terminus which forms a disulphide-linked dimer [8] and a bZip_Maf domain at the C-terminus.

BACH2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3OHU, 3OHV
Identifiers
Aliases	BACH2, BTBD25, BTB domain and CNC homolog 2, IMD60
External IDs	OMIM: 605394 MGI: 894679 HomoloGene: 7240 GeneCards: BACH2
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q15 Start 89,926,528 bp[1] End 90,296,908 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 A5 Start 32,238,804 bp[2] End 32,586,108 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • DNA binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • ubiquitin-protein transferase activity • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cytoplasm • Cul3-RING ubiquitin ligase complex • cell nucleus • cytosol Biological process • regulation of transcription, DNA-templated • negative regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • transcription, DNA-templated • protein ubiquitination • nuclear import Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	60468	12014
Ensembl	ENSG00000112182	ENSMUSG00000040270
UniProt	Q9BYV9	P97303
RefSeq (mRNA)	NM_001170794 NM_021813	NM_001109661 NM_007521
RefSeq (protein)	NP_001164265 NP_068585	NP_001103131
Location (UCSC)	Chr 6: 89.93 – 90.3 Mb	Chr 4: 32.24 – 32.59 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Disease associations

Single nucleotide variants in BACH2 have been linked to a number of autoimmune diseases in humans.[9] Mendelian BACH2-related immunodeficiency and autoimmunity (BRIDA) syndrome in humans is caused by haploinsufficiency of this transcription factor resulting from germline mutations.[10]

Model organisms

Model organisms have been used in the study of BACH2 function. A conditional knockout mouse line called Bach2^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[11] Male and female animals underwent a standardized phenotypic screen[12] to determine the effects of deletion.[13][14][15][16] Additional screens performed: - In-depth immunological phenotyping[17] - in-depth bone and cartilage phenotyping[18]

Bach2 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[12][17]
Peripheral blood leukocytes 6 Weeks	Abnormal
Haematology 6 Weeks	Abnormal
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Abnormal
Auditory brainstem response	Normal
DEXA	Abnormal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Abnormal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Abnormal
Spleen Immunophenotyping	Abnormal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Abnormal
Influenza Challenge	Normal
Trichuris Challenge	Normal

References

1. GRCh38: Ensembl release 89: ENSG00000112182 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040270 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Sasaki S, Ito E, Toki T, Maekawa T, Kanezaki R, Umenai T, Muto A, Nagai H, Kinoshita T, Yamamoto M, Inazawa J, Taketo MM, Nakahata T, Igarashi K, Yokoyama M (August 2000). "Cloning and expression of human B cell-specific transcription factor BACH2 mapped to chromosome 6q15". Oncogene. 19 (33): 3739–49. doi:10.1038/sj.onc.1203716. PMID 10949928.
6. Kamio T, Toki T, Kanezaki R, Sasaki S, Tandai S, Terui K, Ikebe D, Igarashi K, Ito E (November 2003). "B-cell-specific transcription factor BACH2 modifies the cytotoxic effects of anticancer drugs". Blood. 102 (9): 3317–22. doi:10.1182/blood-2002-12-3656. PMID 12829606.
7. "Entrez Gene: BACH2 BTB and CNC homology 1, basic leucine zipper transcription factor 2".
8. Rosbrook GO, Stead MA, Carr SB, Wright SC (January 2012). "The structure of the Bach2 POZ-domain dimer reveals an intersubunit disulfide bond" (PDF). Acta Crystallographica Section D. 68 (Pt 1): 26–34. doi:10.1107/S0907444911048335. PMID 22194330.
9. Shen C, Gao J, Sheng Y, Dou J, Zhou F, Zheng X, Ko R, Tang X, Zhu C, Yin X, Sun L, Cui Y, Zhang X (2016). "Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci". Frontiers in Genetics. 7: 3. doi:10.3389/fgene.2016.00003. PMC 4740779. PMID 26870082.
10. Afzali B, Grönholm J, Vandrovcova J, O'Brien C, Sun HW, Vanderleyden I, et al. (July 2017). "BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency". Nature Immunology. 18 (7): 813–823. doi:10.1038/ni.3753. PMC 5593426. PMID 28530713.
11. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
12. "International Mouse Phenotyping Consortium".
13. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
14. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
15. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
16. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (July 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
17. "Infection and Immunity Immunophenotyping (3i) Consortium".
18. "OBCD Consortium".

Further reading

• Oyake T, Itoh K, Motohashi H, Hayashi N, Hoshino H, Nishizawa M, Yamamoto M, Igarashi K (November 1996). "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". Molecular and Cellular Biology. 16 (11): 6083–95. doi:10.1128/mcb.16.11.6083. PMC 231611. PMID 8887638.
• Kobayashi A, Yamagiwa H, Hoshino H, Muto A, Sato K, Morita M, Hayashi N, Yamamoto M, Igarashi K (March 2000). "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through the BTB/POZ domain". Molecular and Cellular Biology. 20 (5): 1733–46. doi:10.1128/MCB.20.5.1733-1746.2000. PMC 85356. PMID 10669750.
• Hoshino H, Kobayashi A, Yoshida M, Kudo N, Oyake T, Motohashi H, Hayashi N, Yamamoto M, Igarashi K (May 2000). "Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element". The Journal of Biological Chemistry. 275 (20): 15370–6. doi:10.1074/jbc.275.20.15370. PMID 10809773.
• Vieira SA, Deininger MW, Sorour A, Sinclair P, Foroni L, Goldman JM, Melo JV (December 2001). "Transcription factor BACH2 is transcriptionally regulated by the BCR/ABL oncogene". Genes, Chromosomes & Cancer. 32 (4): 353–63. doi:10.1002/gcc.1200. PMID 11746976.
• Muto A, Tashiro S, Tsuchiya H, Kume A, Kanno M, Ito E, Yamamoto M, Igarashi K (June 2002). "Activation of Maf/AP-1 repressor Bach2 by oxidative stress promotes apoptosis and its interaction with promyelocytic leukemia nuclear bodies". The Journal of Biological Chemistry. 277 (23): 20724–33. doi:10.1074/jbc.M112003200. PMID 11923289.
• Takakuwa T, Luo WJ, Ham MF, Sakane-Ishikawa F, Wada N, Aozasa K (March 2004). "Integration of Epstein-Barr virus into chromosome 6q15 of Burkitt lymphoma cell line (Raji) induces loss of BACH2 expression". The American Journal of Pathology. 164 (3): 967–74. doi:10.1016/S0002-9440(10)63184-7. PMC 1614712. PMID 14982850.
• Tashiro S, Muto A, Tanimoto K, Tsuchiya H, Suzuki H, Hoshino H, Yoshida M, Walter J, Igarashi K (April 2004). "Repression of PML nuclear body-associated transcription by oxidative stress-activated Bach2". Molecular and Cellular Biology. 24 (8): 3473–84. doi:10.1128/MCB.24.8.3473-3484.2004. PMC 381671. PMID 15060166.
• Motamed-Khorasani A, Jurisica I, Letarte M, Shaw PA, Parkes RK, Zhang X, Evangelou A, Rosen B, Murphy KJ, Brown TJ (January 2007). "Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression". Oncogene. 26 (2): 198–214. doi:10.1038/sj.onc.1209773. PMID 16832351.
• Yoshida C, Yoshida F, Sears DE, Hart SM, Ikebe D, Muto A, Basu S, Igarashi K, Melo JV (February 2007). "Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1". Blood. 109 (3): 1211–9. doi:10.1182/blood-2005-12-040972. PMID 17018862. S2CID 10475263.
• Ono A, Kono K, Ikebe D, Muto A, Sun J, Kobayashi M, Ueda K, Melo JV, Igarashi K, Tashiro S (January 2007). "Nuclear positioning of the BACH2 gene in BCR-ABL positive leukemic cells". Genes, Chromosomes & Cancer. 46 (1): 67–74. doi:10.1002/gcc.20390. PMID 17044046.
• Ikeda T, Shibata J, Yoshimura K, Koito A, Matsushita S (March 2007). "Recurrent HIV-1 integration at the BACH2 locus in resting CD4+ T cell populations during effective highly active antiretroviral therapy". The Journal of Infectious Diseases. 195 (5): 716–25. doi:10.1086/510915. PMID 17262715.
• Hoshino H, Nishino TG, Tashiro S, Miyazaki M, Ohmiya Y, Igarashi K, Horinouchi S, Yoshida M (May 2007). "Co-repressor SMRT and class II histone deacetylases promote Bach2 nuclear retention and formation of nuclear foci that are responsible for local transcriptional repression". Journal of Biochemistry. 141 (5): 719–27. CiteSeerX 10.1.1.326.4123. doi:10.1093/jb/mvm073. PMID 17383980.

External links

• BACH2+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human BACH2 genome location and BACH2 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q9BYV9 (Transcription regulator protein BACH2) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.