BCL11A

BCL11A
Identifiers
Aliases	BCL11A, BCL11A-L, BCL11A-S, BCL11A-XL, BCL11a-M, CTIP1, EVI9, HBFQTL5, ZNF856, B-cell CLL/lymphoma 11A, DILOS, B cell CLL/lymphoma 11A, BAF complex component, BAF chromatin remodeling complex subunit BCL11A
External IDs	OMIM: 606557 MGI: 106190 HomoloGene: 11284 GeneCards: BCL11A
Gene location (Human)
Chr.	Chromosome 2 (human)[1]
End	60,554,467 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	24,174,123 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	• protein homodimerization activity; • metal ion binding; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • GO:0001948 protein binding; • protein heterodimerization activity; • 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; • protein kinase binding; • sequence-specific DNA binding;
Cellular component	• cytoplasm; • nucleoplasm; • cell nucleus; • GO:0097483, GO:0097481 postsynaptic density;
Biological process	• negative regulation of protein homooligomerization; • negative regulation of neuron projection development; • regulation of transcription, DNA-templated; • regulation of dendrite development; • negative regulation of transcription from RNA polymerase II promoter; • positive regulation of collateral sprouting; • protein sumoylation; • transcription, DNA-templated; • negative regulation of collateral sprouting; • positive regulation of neuron projection development; • negative regulation of axon extension; • signal transduction; • positive regulation of transcription from RNA polymerase II promoter; • neurogenesis; • negative regulation of dendrite development; • positive regulation of gene expression; • negative regulation of dendrite extension; • negative regulation of neuron remodeling; • cellular response to L-glutamate; • negative regulation of branching morphogenesis of a nerve;
	Sources:Amigo / QuickGO
Orthologs
	53335
	14025
	ENSG00000119866
	ENSMUSG00000000861
	Q9H165
	Q9QYE3
NM_018014; NM_022893; NM_138553; NM_138559; NM_001363864;
	NM_001365609
	NM_001159289; NM_001159290; NM_001242934; NM_016707
	NP_060484; NP_075044; NP_612569; NP_001350793; NP_001352538
	NP_001152761; NP_001152762; NP_001229863; NP_057916
	Wikidata
View/Edit Human	View/Edit Mouse

B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the BCL11A gene.[5][6][7]

Function

The BCL11A gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been reported.[7] The protein associates with the SWI/SNF complex, that regulates gene expression via chromatin remodelling.[8]

BCL11A is highly expressed in several hematopoietic lineages, and plays a role in the switch from γ- to β-globin expression during the fetal to adult erythropoiesis transition.[9]

Furthermore, BCL11A is expressed in the brain, where it forms a protein complex with CASK to regulate axon outgrowth and branching.[10] In the neocortex, BCL11A binds to the TBR1 regulatory region and inhibits the expression of TBR1.[11]

Clinical significance

The corresponding Bcl11a mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. In addition, BCL11A has been found to play a role in the suppression of fetal hemoglobin production. Therapeutic strategies aimed at increasing fetal globin production in diseases such as beta thalassemia and sickle cell anemia by inhibiting BCL11A are currently being explored.

Furthermore, heterozygous de novo mutations in BCL11A have been identified in an intellectual disability disorder, accompanied with global developmental delay and autism spectrum disorder.[12] These mutations disrupt BCL11A homodimerization and transcriptional regulation.

BCL11A has also been identified as an important gene of interest in type-2 diabetes. Methylation of BCl11A has been hypothesized to contribute to type-2 diabetes risk, while BCL11a loss in a human islet model was demonstrated to result in an increase in insulin secretion. [13][14]

Interactions

BCL11A has been shown to interact with a number of proteins. BCL11A was initially discovered as a COUP-TFI interacting protein.[15] In the nucleus, BCL11A forms paraspeckles that co-localize with NONO.[12] In neurons, BCL11A interacts with CASK to regulate target genes.[10] Furthermore, BCL11A interacts with the neuron-specific protein TBR1, which is also implicated in intellectual disability and autism spectrum disorder.[16]

References

GRCh38: Ensembl release 89: ENSG00000119866 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000000861 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ (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.
Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, et al. (February 2008). "Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia". Proceedings of the National Academy of Sciences of the United States of America. 105 (5): 1620–5. Bibcode:2008PNAS..105.1620U. doi:10.1073/pnas.0711566105. PMC 2234194. PMID 18245381.
"Entrez Gene: BCL11A B-cell CLL/lymphoma 11A (zinc finger protein)".
Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR (June 2013). "Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy". Nature Genetics. 45 (6): 592–601. doi:10.1038/ng.2628. PMC 3667980. PMID 23644491.
Smith EC, Luc S, Croney DM, Woodworth MB, Greig LC, Fujiwara Y, Nguyen M, Sher F, Macklis JD, Bauer DE, Orkin SH (November 2016). "Bcl11a erythroid enhancer". Blood. 128 (19): 2338–2342. doi:10.1182/blood-2016-08-736249. PMC 5106112. PMID 27707736.
Kuo TY, Hong CJ, Chien HL, Hsueh YP (August 2010). "X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth". Journal of Neuroscience Research (in German). 88 (11): 2364–73. doi:10.1002/jnr.22407. PMID 20623620. S2CID 19810502.
Cánovas J, Berndt FA, Sepúlveda H, Aguilar R, Veloso FA, Montecino M, Oliva C, Maass JC, Sierralta J, Kukuljan M (May 2015). "The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a". The Journal of Neuroscience. 35 (19): 7552–64. doi:10.1523/JNEUROSCI.0169-15.2015. PMC 6705430. PMID 25972180.
Dias C, Estruch SB, Graham SA, McRae J, Sawiak SJ, Hurst JA, Joss SK, Holder SE, Morton JE, Turner C, Thevenon J, Mellul K, Sánchez-Andrade G, Ibarra-Soria X, Deriziotis P, Santos RF, Lee SC, Faivre L, Kleefstra T, Liu P, Hurles ME, Fisher SE, Logan DW (August 2016). "BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription". American Journal of Human Genetics. 99 (2): 253–74. doi:10.1016/j.ajhg.2016.05.030. PMC 4974071. PMID 27453576.
Heshan Peiris, Sangbin Park, Shreya Louis, Xueying Gu, Jonathan Y Lam, Olof Asplund, Gregory C Ippolito, Rita Bottino, Leif Groop, Haley Tucker, Seung K Kim (September 2018). "Discovering human diabetes-risk gene function with genetics and physiological assays". Nature Communications. 9 (1): 1–11. doi:10.1038/s41467-018-06249-3.CS1 maint: uses authors parameter (link)
Tang L, Wang L, Ye H, Xu X, Hong Q, Wang H, et al. (August 2014). "BCL11A gene DNA methylation contributes to the risk of type 2 diabetes in males". Experimental and Therapeutic Medicine. 8 (2): 459–463. doi:10.3892/etm.2014.1783. PMID 25009601.
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.
den Hoed J, Sollis E, Venselaar H, Estruch SB, Deriziotis P, Fisher SE (September 2018). "Functional characterization of TBR1 variants in neurodevelopmental disorder". Scientific Reports. 8 (1): 14279. Bibcode:2018NatSR...814279D. doi:10.1038/s41598-018-32053-6. PMC 6155134. PMID 30250039.

External links

BCL11A+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
FactorBook BCL11A
Human BCL11A genome location and BCL11A 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.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000119866 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000000861 - 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.

[pmid11719382-5] Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ (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.

[pmid18245381-6] Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, et al. (February 2008). "Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia". Proceedings of the National Academy of Sciences of the United States of America. 105 (5): 1620–5. Bibcode:2008PNAS..105.1620U. doi:10.1073/pnas.0711566105. PMC 2234194. PMID 18245381.

[entrez-7] "Entrez Gene: BCL11A B-cell CLL/lymphoma 11A (zinc finger protein)".

[8] Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR (June 2013). "Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy". Nature Genetics. 45 (6): 592–601. doi:10.1038/ng.2628. PMC 3667980. PMID 23644491.

[9] Smith EC, Luc S, Croney DM, Woodworth MB, Greig LC, Fujiwara Y, Nguyen M, Sher F, Macklis JD, Bauer DE, Orkin SH (November 2016). "Bcl11a erythroid enhancer". Blood. 128 (19): 2338–2342. doi:10.1182/blood-2016-08-736249. PMC 5106112. PMID 27707736.

[:0-10] Kuo TY, Hong CJ, Chien HL, Hsueh YP (August 2010). "X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth". Journal of Neuroscience Research (in German). 88 (11): 2364–73. doi:10.1002/jnr.22407. PMID 20623620. S2CID 19810502.

[11] Cánovas J, Berndt FA, Sepúlveda H, Aguilar R, Veloso FA, Montecino M, Oliva C, Maass JC, Sierralta J, Kukuljan M (May 2015). "The Specification of Cortical Subcerebral Projection Neurons Depends on the Direct Repression of TBR1 by CTIP1/BCL11a". The Journal of Neuroscience. 35 (19): 7552–64. doi:10.1523/JNEUROSCI.0169-15.2015. PMC 6705430. PMID 25972180.

[:1-12] Dias C, Estruch SB, Graham SA, McRae J, Sawiak SJ, Hurst JA, Joss SK, Holder SE, Morton JE, Turner C, Thevenon J, Mellul K, Sánchez-Andrade G, Ibarra-Soria X, Deriziotis P, Santos RF, Lee SC, Faivre L, Kleefstra T, Liu P, Hurles ME, Fisher SE, Logan DW (August 2016). "BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription". American Journal of Human Genetics. 99 (2): 253–74. doi:10.1016/j.ajhg.2016.05.030. PMC 4974071. PMID 27453576.

[13] Heshan Peiris, Sangbin Park, Shreya Louis, Xueying Gu, Jonathan Y Lam, Olof Asplund, Gregory C Ippolito, Rita Bottino, Leif Groop, Haley Tucker, Seung K Kim (September 2018). "Discovering human diabetes-risk gene function with genetics and physiological assays". Nature Communications. 9 (1): 1–11. doi:10.1038/s41467-018-06249-3.CS1 maint: uses authors parameter (link)

[14] Tang L, Wang L, Ye H, Xu X, Hong Q, Wang H, et al. (August 2014). "BCL11A gene DNA methylation contributes to the risk of type 2 diabetes in males". Experimental and Therapeutic Medicine. 8 (2): 459–463. doi:10.3892/etm.2014.1783. PMID 25009601.

[15] 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.

[16] Hoed J, Sollis E, Venselaar H, Estruch SB, Deriziotis P, Fisher SE (September 2018). "Functional characterization of TBR1 variants in neurodevelopmental disorder". Scientific Reports. 8 (1): 14279. Bibcode:2018NatSR...814279D. doi:10.1038/s41598-018-32053-6. PMC 6155134. PMID 30250039.