Atlas of Genetics and Cytogenetics in Oncology and Haematology


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BCL11B (B-cell lymphoma/leukaemia 11B)

Identity

Other namesCTIP2 (Ctip-2) chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein
Rit1 zinc finger protein hRit1 alpha (not to be confused with RIT1 on chr. 1q22)
HGNC (Hugo) BCL11B
LocusID (NCBI) 64919
Location 14q32.2
Location_base_pair Starts at 99635625 and ends at 99737822 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
Note BCL11B (14q32.2): FISH with RP11 BAC clones 1127d7 (green label) and 1057p17 (red label) showing split signal as indicated above right (dotted lines). Observe telomeric part of chr 14 translocated to the der(5) as revealed by the red doublet signal. The der(14) partner in turn receives a microinsertion containing material from chr 5. Analysis was performed on the pediatric T-ALL cell line CCRF-CEM which carries t(5;14)(q35.1;q32) resulting in ectopic expression of of NKX2-5 (2Mbp telomeric of, and closely related to, the standard partner gene TLX3 at 5q35) by juxtaposition with the far downstream region of BCL11B.

DNA/RNA

 
Description ORF comprises 4 exons, exon 3 being alternately spliced, while the 3' part of exon 4 is untranslated. Alternative splice variants due to presence (var.1) or absence (var.2) of exon 3.
Transcription In a telomeric --> centromeric orientation.

Protein

 
Description 894 amino acids, 95.5 kDa; contains 6 krueppel-like Zn-finger domains and a proline-rich region
Expression Normal expression in thymus and brain; malignant expression in T-cell neoplasia and Ewing-family tumors.
Localisation Inner nuclear membrane; colocalization with heterochromatin protein (HP1) and histone deacetylase SIRT1 suggests role as transcriptional repressor.
Function Poorly defined; transcriptional repressor; developmentally regulates thymic differentiation and survival; inhibits HIV-1 Tat transactivation and repression of viral replication.
Homology BCL11A on chromosome 2p13.

Mutations

Somatic Unrecorded in humans. Biallelic mutation/deletion in mouse thymic lymphomas induced by ionizing radiation.

Implicated in

Entity T-cell acute lymphoblastic leukemia (T-ALL) with t(5;14)(q35;q32) --> TLX3 - BCL11B
Disease First detected as translocation partner of TLX3 (alias HOX11L2) in 15-20% pediatric cortical T-ALL with possible male bias; subsequently confirmed in adult T-ALL, albeit less frequently.
Prognosis May be poor via strong cytogenetic assocation with TLX3 which reportedly confers adverse prognosis.
Cytogenetics Additional known recurrent rearrangements reportedly absent from t(5;14) patients.
Oncogenesis Distal regulatory elements drive ectopic expression of TLX3 in T-ALL and possibly other related NK-family Hox genes, viz. NKX2-5. Tumor suppressor role reported in mouse yet to be confirmed in man.
  

Breakpoints

 
 
Note t(5;14) breakpoints are widely scattered over 1.2 Mbp downstream of BCL11B probably targeting distal enhancer(s) posited to lie in the "gene desert" separating BCL11b from VRK1. This region has been recently shown to carry multiple Dnase-I sensitive sites in T-cells which may represent a locus control region. The solitary AML breakpoint lies upstream of BCL11B and its significance has yet to be established.

External links

Nomenclature
HGNC (Hugo)BCL11B   13222
Entrez_Gene (NCBI)BCL11B  64919  B-cell CLL/lymphoma 11B (zinc finger protein)
Cards
AtlasBCL11BID392
GeneCards (Weizmann)BCL11B
Ensembl (Hinxton)ENSG00000127152 [Gene_View]  chr14:99635625-99737822 [Contig_View]  BCL11B [Vega]
AceView (NCBI)BCL11B
Genatlas (Paris)BCL11B
euGene (Indiana)64919
SOURCE (Stanford)NM_022898 NM_138576
Genomic and cartography
GoldenPath (UCSC)BCL11B  -  14q32.2   chr14:99635625-99737822 -  14q32.2   [Description]    (hg19-Feb_2009)
EnsemblBCL11B - 14q32.2 [CytoView]
Mapping of homologs : NCBIBCL11B [Mapview]
OMIM606558   
Gene and transcription
Genbank (Entrez)AB043584 AF086271 AJ404614 BC156139
RefSeq transcript (SRS)NM_022898 NM_138576
RefSeq transcript (Entrez)NM_022898 NM_138576
RefSeq genomic (SRS)AC_000146 NC_000014 NG_027894 NT_026437 NW_001838115
RefSeq genomic (Entrez)AC_000146 NC_000014 NG_027894 NT_026437 NW_001838115
Consensus coding sequences : CCDS (NCBI)BCL11B
Cluster EST : UnigeneHs.709690 [ SRS ] Hs.709690 [ NCBI ]
Alternative Splicing : Fast-db (Paris)5545
Alternative Splicing GalleryENSG00000127152
Gene ExpressionBCL11B [ NCBI-GEO ]   BCL11B [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9C0K0 (SRS) Q9C0K0 (Uniprot)
With graphics : InterProQ9C0K0
Splice isoforms : SwissVarQ9C0K0(Swissvar)
Domaine pattern : Prosite (SRS)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (SRS)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Related proteins : CluSTrQ9C0K0
Domain families : Pfam (SRS)zf-C2H2 (PF00096)   
Domain families : Pfam (Sanger)zf-C2H2 (PF00096)   
Domain families : Pfam (NCBI)pfam00096   
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
Blocks (Seattle)Q9C0K0
Human Protein AtlasENSG00000127152
HPRD05950
IPIIPI00009213   IPI00009646   IPI00853567   
Protein Interaction databases
DIP (DOE-UCLA)Q9C0K0
IntAct (EBI)Q9C0K0
FunCoupENSG00000127152
REACTOMEBCL11B
BioGRIDBCL11B
InParanoidQ9C0K0
Interologous Interaction database Q9C0K0
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)BCL11B
SNP (GeneSNP Utah)BCL11B
SNP : HGBaseBCL11B
Genetic variants : HAPMAPBCL11B
Cancer Gene: CensusBCL11B 
Somatic Mutations in Cancer : COSMICBCL11B 
CONAN: Copy Number AnalysisBCL11B 
Translocation Breakpoints in Cancer : TICdbBCL11B 
Mutations and Diseases : HGMDBCL11B
OMIM606558   
GENETests606558   
Disease Genetic AssociationBCL11B
Huge Navigator BCL11B [HugePedia]  BCL11B [HugeCancerGEM]
Genomic VariantsBCL11B
snp3D : Map Gene to Disease64919
General knowledge
Homologs : HomoloGeneBCL11B
Homology/Alignments : Family Browser (UCSC)BCL11B
Phylogenetic Trees/Animal Genes : TreeFamBCL11B
Chemical/Protein Interactions : CTD64919
Chemical/Pharm GKB GenePA25301
Clinical trialBCL11B
Cancer Resource (Charite)ENSG00000127152
Ontology : AmiGORNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  keratinocyte development  epithelial cell morphogenesis  nucleic acid binding  intracellular  nucleus  regulation of transcription, DNA-dependent  axonogenesis  zinc ion binding  negative regulation of cell proliferation  regulation of keratinocyte proliferation  regulation of lipid metabolic process  striatal medium spiny neuron differentiation  central nervous system neuron differentiation  post-embryonic camera-type eye development  T cell differentiation in thymus  T cell receptor V(D)J recombination  odontogenesis of dentin-containing tooth  negative regulation of apoptotic process  positive T cell selection  sequence-specific DNA binding  skin development  positive regulation of transcription from RNA polymerase II promoter  alpha-beta T cell differentiation  metal ion binding  thymus development  
Ontology : EGO-EBIRNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  keratinocyte development  epithelial cell morphogenesis  nucleic acid binding  intracellular  nucleus  regulation of transcription, DNA-dependent  axonogenesis  zinc ion binding  negative regulation of cell proliferation  regulation of keratinocyte proliferation  regulation of lipid metabolic process  striatal medium spiny neuron differentiation  central nervous system neuron differentiation  post-embryonic camera-type eye development  T cell differentiation in thymus  T cell receptor V(D)J recombination  odontogenesis of dentin-containing tooth  negative regulation of apoptotic process  positive T cell selection  sequence-specific DNA binding  skin development  positive regulation of transcription from RNA polymerase II promoter  alpha-beta T cell differentiation  metal ion binding  thymus development  
Other databases
Probes
Probes : ImagenesBCL11B Related clones (RZPD - Berlin)
Litterature
PubMed26 Pubmed reference(s) in Entrez
PubGeneBCL11B
iHOPBCL11B

Bibliography

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COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein.
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Activation of HOX11L2 by juxtaposition with 3'-BCL11B in an acute lymphoblastic leukemia cell line (HPB-ALL) with t(5;14)(q35;q32.2).
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The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2).
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Bcl11b is required for differentiation and survival of alphabeta T lymphocytes.
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A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene.
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Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951.
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Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites.
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BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia.
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Involvement of V(D)J recombinase in the generation of intragenic deletions in the Rit1/Bcl11b tumor suppressor gene in gamma-ray-induced thymic lymphomas and in normal thymus of the mouse.
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REVIEW articlesautomatic search in PubMed
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Contributor(s)

Written07-2004Roderick A F MacLeod, Stefan Nagel
DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen, Mascheroder Weg 1b 38124, Braunschweig, Germany

Citation

This paper should be referenced as such :
MacLeod RAF, Nagel S . BCL11B (B-cell lymphoma/leukaemia 11B). Atlas Genet Cytogenet Oncol Haematol. July 2004 .
URL : http://AtlasGeneticsOncology.org/Genes/BCL11BID392.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38107/1/07-2004-BCL11BID392.pdf   [ Bibliographic record ]

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