BCL11B

B-cell lymphoma/leukemia 11B is a protein that in humans is encoded by the BCL11B gene.[5][6][7]

BCL11B
Identifiers
Aliases	BCL11B, ATL1, ATL1-alpha, ATL1-beta, ATL1-delta, ATL1-gamma, CTIP-2, CTIP2, RIT1, ZNF856B, hRIT1-alpha, B-cell CLL/lymphoma 11B, IMD49, B cell CLL/lymphoma 11B, IDDFSTA, BAF complex component, BAF chromatin remodeling complex subunit BCL11B
External IDs	OMIM: 606558 MGI: 1929913 HomoloGene: 10974 GeneCards: BCL11B
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q32.2 Start 99,169,287 bp[1] End 99,272,197 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 F1|12 59.1 cM Start 107,910,403 bp[2] End 108,003,602 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • metal ion binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001948 protein binding • nucleic acid binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity Cellular component • intracellular • neuron projection • cell nucleus Biological process • commitment of neuronal cell to specific neuron type in forebrain • regulation of neuron differentiation • neurogenesis • olfactory bulb axon guidance • regulation of transcription, DNA-templated • T cell differentiation in thymus • axonogenesis • epithelial cell morphogenesis • thymus development • T cell receptor V(D)J recombination • negative regulation of apoptotic process • transcription from RNA polymerase II promoter • post-embryonic development • positive T cell selection • transcription, DNA-templated • striatal medium spiny neuron differentiation • odontogenesis of dentin-containing tooth • regulation of lipid metabolic process • keratinocyte development • post-embryonic camera-type eye development • central nervous system neuron differentiation • regulation of gene expression • alpha-beta T cell differentiation • regulation of keratinocyte proliferation • signal transduction • negative regulation of cell proliferation • positive regulation of transcription from RNA polymerase II promoter • skin development • hematopoietic stem cell migration • lymphoid lineage cell migration into thymus Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	64919	58208
Ensembl	ENSG00000127152	ENSMUSG00000048251
UniProt	Q9C0K0	Q99PV8
RefSeq (mRNA)	NM_001282237 NM_001282238 NM_022898 NM_138576	NM_001079883 NM_001286343 NM_021399
RefSeq (protein)	NP_001269166 NP_001269167 NP_075049 NP_612808	NP_001073352 NP_001273272 NP_067374
Location (UCSC)	Chr 14: 99.17 – 99.27 Mb	Chr 12: 107.91 – 108 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Gene location

BCL11B is located on human chromosome 14p32.2.[8] The mouse analogue is called Rit1 or Bcl11b and is located on mouse chromosome 12.[9]

Function

This gene encodes a C2H2-type zinc finger protein and is closely related to BCL11A, a gene whose translocation may be associated with B-cell malignancies. The specific function of this gene has not yet been determined, but it could also be involved in some malignancies. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported.[7]

Recent research suggests that BCL11B is crucial for ameloblasts (the cells that produce tooth enamel) to form and work properly.[10]

Interactions

BCL11B has been shown to interact with COUP-TFI.[11]

Pathology

BCL11B is closely connected with immune regulation and for so its mutation can lead to a SCID phenotype. This so-called Immunodeficiency 49 (OMIM #617237) is classified as T-B+NK+ SCID.[12] It is characterised by a lack of T lymphocytes and its malfunctioning specifically in proliferative response. On the other hand, B cells and NK cells counts and functions are not impaired.[13] The symptoms of SCID caused by BCL11B mutation - apart from immunity defects - typically include teeth abnormalities, craniofacial dimorphism, different types of dermatitis. As well the intellectual development is significantly impaired. The disease has a very early onset and the only known treatment is hematopoietic stem cell transplantation from a healthy donor.[14][13] The immunodeficiency has a dominant negative mode of inheritance as all so far described patients suffering from it has been after sequencing identified as heterozygotes in the BCL11B gene.[13][14]

Research projects

A mouse model based study showed, that Bcl11b also plays an important role in pathogenesis of inflammatory bowel disease. Bcl11b gene knock-out in certain T cell population led to development of IBD. The mechanisms behind are supposed to be reduced suppressor activity of T regulatory cells and changes in cytokine environment. Bcl11b is suspected to interact with Foxp3 and IL10 gene promoters and thus impair its suppressive function in the intestines.[15]

Bcl11b (mouse analogue of human BCL11B) has been proven to contribute to malignant growth for example in case of mouse lymphomas. That is suspected to be caused by interaction with p53, a well-known tumor suppressor gene.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000127152 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000048251 - 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. Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, et al. (December 2001). "The BCL11 gene family: involvement of BCL11A in lymphoid malignancies". Blood. 98 (12): 3413–20. doi:10.1182/blood.V98.12.3413. PMID 11719382.
6. Topark-Ngarm A, Golonzhka O, Peterson VJ, Barrett B, Martinez B, Crofoot K, et al. (October 2006). "CTIP2 associates with the NuRD complex on the promoter of p57KIP2, a newly identified CTIP2 target gene". The Journal of Biological Chemistry. 281 (43): 32272–83. doi:10.1074/jbc.M602776200. PMC 2547407. PMID 16950772.
7. "Entrez Gene: BCL11B B-cell CLL/lymphoma 11B (zinc finger protein)".
8. "OMIM Entry - * 606558 - B-CELL CLL/LYMPHOMA 11B; BCL11B". www.omim.org. Retrieved 2019-07-29.
9. Wakabayashi Y, Inoue J, Takahashi Y, Matsuki A, Kosugi-Okano H, Shinbo T, et al. (February 2003). "Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas". Biochemical and Biophysical Research Communications. 301 (2): 598–603. doi:10.1016/S0006-291X(02)03069-3. PMID 12565905.
10. Golonzhka O, Metzger D, Bornert JM, Bay BK, Gross MK, Kioussi C, Leid M (March 2009). "Ctip2/Bcl11b controls ameloblast formation during mammalian odontogenesis". Proceedings of the National Academy of Sciences of the United States of America. 106 (11): 4278–83. Bibcode:2009PNAS..106.4278G. doi:10.1073/pnas.0900568106. PMC 2657370. PMID 19251658. Lay summary – BBC News.
11. Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M (April 2000). "Isolation of a novel family of C(2)H(2) zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors". The Journal of Biological Chemistry. 275 (14): 10315–22. doi:10.1074/jbc.275.14.10315. PMC 2819356. PMID 10744719.
12. Advances in immunology. Volume 138. Alt, Frederick W. Cambridge, MA. ISBN 9780128155295. OCLC 1035016036.CS1 maint: others (link)
13. Punwani D, Zhang Y, Yu J, Cowan MJ, Rana S, Kwan A, et al. (December 2016). "Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B". The New England Journal of Medicine. 375 (22): 2165–2176. doi:10.1056/nejmoa1509164. PMC 5215776. PMID 27959755.
14. Lessel D, Gehbauer C, Bramswig NC, Schluth-Bolard C, Venkataramanappa S, van Gassen KL, et al. (August 2018). "BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells". Brain. 141 (8): 2299–2311. doi:10.1093/brain/awy173. PMC 6061686. PMID 29985992.
15. Vanvalkenburgh J, Albu DI, Bapanpally C, Casanova S, Califano D, Jones DM, et al. (September 2011). "Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease". The Journal of Experimental Medicine. 208 (10): 2069–81. doi:10.1084/jem.20102683. PMC 3182057. PMID 21875956.

Further reading

• Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M (April 2000). "Isolation of a novel family of C(2)H(2) zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors". The Journal of Biological Chemistry. 275 (14): 10315–22. doi:10.1074/jbc.275.14.10315. PMC 2819356. PMID 10744719.
• Avram D, Fields A, Senawong T, Topark-Ngarm A, Leid M (December 2002). "COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein". The Biochemical Journal. 368 (Pt 2): 555–63. doi:10.1042/BJ20020496. PMC 1223006. PMID 12196208.
• Wakabayashi Y, Inoue J, Takahashi Y, Matsuki A, Kosugi-Okano H, Shinbo T, et al. (February 2003). "Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas". Biochemical and Biophysical Research Communications. 301 (2): 598–603. doi:10.1016/S0006-291X(02)03069-3. PMID 12565905.
• Rohr O, Lecestre D, Chasserot-Golaz S, Marban C, Avram D, Aunis D, et al. (May 2003). "Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells". Journal of Virology. 77 (9): 5415–27. doi:10.1128/JVI.77.9.5415-5427.2003. PMC 153947. PMID 12692243.
• Senawong T, Peterson VJ, Avram D, Shepherd DM, Frye RA, Minucci S, Leid M (October 2003). "Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression". The Journal of Biological Chemistry. 278 (44): 43041–50. doi:10.1074/jbc.M307477200. PMC 2819354. PMID 12930829.
• Bezrookove V, van Zelderen-Bhola SL, Brink A, Szuhai K, Raap AK, Barge R, et al. (February 2004). "A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene". Cancer Genetics and Cytogenetics. 149 (1): 72–6. doi:10.1016/S0165-4608(03)00302-9. PMID 15104287.
• MacLeod RA, Nagel S, Drexler HG (August 2004). "BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia". Cancer Genetics and Cytogenetics. 153 (1): 88–9. doi:10.1016/j.cancergencyto.2004.02.020. PMID 15325104.
• Przybylski GK, Dik WA, Wanzeck J, Grabarczyk P, Majunke S, Martin-Subero JI, et al. (February 2005). "Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL". Leukemia. 19 (2): 201–8. doi:10.1038/sj.leu.2403619. PMID 15668700.
• Cismasiu VB, Adamo K, Gecewicz J, Duque J, Lin Q, Avram D (October 2005). "BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter". Oncogene. 24 (45): 6753–64. doi:10.1038/sj.onc.1208904. PMID 16091750.
• Marban C, Suzanne S, Dequiedt F, de Walque S, Redel L, Van Lint C, et al. (January 2007). "Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing". The EMBO Journal. 26 (2): 412–23. doi:10.1038/sj.emboj.7601516. PMC 1783449. PMID 17245431.
• Nagel S, Scherr M, Kel A, Hornischer K, Crawford GE, Kaufmann M, et al. (February 2007). "Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1". Cancer Research. 67 (4): 1461–71. doi:10.1158/0008-5472.CAN-06-2615. PMID 17308084.
• Kamimura K, Mishima Y, Obata M, Endo T, Aoyagi Y, Kominami R (August 2007). "Lack of Bcl11b tumor suppressor results in vulnerability to DNA replication stress and damages". Oncogene. 26 (40): 5840–50. doi:10.1038/sj.onc.1210388. PMID 17369851.

External links

• BCL11B+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human ATL1 genome location and ATL1 gene details page in the UCSC Genome Browser.
• Human BCL11B genome location and BCL11B gene details page in the UCSC Genome Browser.
• Human RIT1 genome location and RIT1 gene details page in the UCSC Genome Browser.

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