BCL11B (B-cell lymphoma/leukaemia 11B)

2004-07-01 Roderick A F MacLeod , Stefan Nagel Affiliation

DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen, Mascheroder Weg 1b 38124, Braunschweig, Germany

Identity

HGNC

BCL11B

LOCATION

14q32.2

IMAGE

LOCUSID

64919

ALIAS

ATL1,ATL1-alpha,ATL1-beta,ATL1-delta,ATL1-gamma,CTIP-2,CTIP2,IDDFSTA,IMD49,RIT1,ZNF856B,hRIT1-alpha

FUSION GENES

Show Gene Fusions

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.

Proteins

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 name

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.

Bibliography

Pubmed ID	Last Year	Title	Authors
12196208	2002	COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein.	Avram D et al
11587205	2001	A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.	Bernard OA et al
15104287	2004	A novel t(6;14)(q25-q27;q32) in acute myelocytic leukemia involves the BCL11B gene.	Bezrookove V et al
14504110	2004	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.	Cavé H et al
14732688	2004	Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites.	Crawford GE et al
15325104	2004	BCL11B rearrangements probably target T-cell neoplasia rather than acute myelocytic leukemia.	MacLeod RA et al
14500364	2003	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).	Nagel S et al
12692243	2003	Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells.	Rohr O et al
14754877	2004	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.	Sakata J et al
11719382	2001	The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.	Satterwhite E et al
12930829	2003	Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression.	Senawong T et al
14697215	2004	Two distinct methods analyzing chromatin structure using centrifugation and antibodies to modified histone H3: both provide similar chromatin states of the Rit1/Bcl11b gene.	Togashi T et al
12717433	2003	Bcl11b is required for differentiation and survival of alphabeta T lymphocytes.	Wakabayashi Y et al
15194534	2004	Two dual-color split signal fluorescence in situ hybridization assays to detect t(5;14) involving HOX11L2 or CSX in T-cell acute lymphoblastic leukemia.	van Zutven LJ et al

Other Information

Locus ID:

NCBI: 64919
MIM: 606558
HGNC: 13222
Ensembl: ENSG00000127152

Variants:

dbSNP: 64919
ClinVar: 64919
TCGA: ENSG00000127152
COSMIC: BCL11B

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000127152	ENST00000345514	Q9C0K0
ENSG00000127152	ENST00000345514	L8B567
ENSG00000127152	ENST00000357195	Q9C0K0
ENSG00000127152	ENST00000357195	L8B7P7
ENSG00000127152	ENST00000443726	D3YTK1

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
17245431	2007	Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing.	165
16091750	2005	BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter.	68
21878675	2011	The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia.	65
12930829	2003	Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression.	53
19581932	2009	p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1.	51
22068335	2012	Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.	34
23852730	2013	CTIP2 is a negative regulator of P-TEFb.	34
15668700	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.	33
18595722	2008	Functional roles for the striatal-enriched transcription factor, Bcl11b, in the control of striatal gene expression and transcriptional dysregulation in Huntington's disease.	31
17308084	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.	28

Citation

Roderick A F MacLeod ; Stefan Nagel

BCL11B (B-cell lymphoma/leukaemia 11B)

Atlas Genet Cytogenet Oncol Haematol. 2004-07-01

Online version: http://atlasgeneticsoncology.org/gene/392/bcl11bid392