BCL11A

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 remodeling.^[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

Furthermore, heterozygous de novo mutations in BCL11A have been identified in an intellectual disability disorder, accompanied with global developmental delay and autism spectrum disorder.^[14] 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.^[15][16]

Interactions

BCL11A has been shown to interact with a number of proteins. BCL11A was initially discovered as a

Further reading

• Sanger Centre, The; Washington University Genome Sequencing Cente, The (November 1998). "Toward a complete human genome sequence". Genome Research. 8 (11): 1097–108.
  PMID 9847074
  .
• 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.
  PMID 10744719
  .
• Nakamura T, Yamazaki Y, Saiki Y, Moriyama M, Largaespada DA, Jenkins NA, Copeland NG (May 2000). "Evi9 encodes a novel zinc finger protein that physically interacts with BCL6, a known human B-cell proto-oncogene product". Molecular and Cellular Biology. 20 (9): 3178–86.
  PMID 10757802
  .
• Saiki Y, Yamazaki Y, Yoshida M, Katoh O, Nakamura T (December 2000). "Human EVI9, a homologue of the mouse myeloid leukemia gene, is expressed in the hematopoietic progenitors and down-regulated during myeloid differentiation of HL60 cells". Genomics. 70 (3): 387–91.
  PMID 11161790
  .
• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95.
  PMID 11347906
  .
• Martín-Subero JI, Gesk S, Harder L, Sonoki T, Tucker PW, Schlegelberger B, Grote W, Novo FJ, Calasanz MJ, Hansmann ML, Dyer MJ, Siebert R (February 2002). "Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma". Blood. 99 (4): 1474–7.
  PMID 11830502
  .
• Küppers R, Sonoki T, Satterwhite E, Gesk S, Harder L, Oscier DG, Tucker PW, Dyer MJ, Siebert R (May 2002). "Lack of somatic hypermutation of IG V(H) genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene". Leukemia. 16 (5): 937–9.
  PMID 11986957
  .
• Senawong T, Peterson VJ, Leid M (February 2005). "BCL11A-dependent recruitment of SIRT1 to a promoter template in mammalian cells results in histone deacetylation and transcriptional repression". Archives of Biochemistry and Biophysics. 434 (2): 316–25.
  PMID 15639232
  .
• Liu H, Ippolito GC, Wall JK, Niu T, Probst L, Lee BS, Pulford K, Banham AH, Stockwin L, Shaffer AL, Staudt LM, Das C, Dyer MJ, Tucker PW (May 2006). "Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells". Molecular Cancer. 5: 18.
  PMID 16704730
  .
• Weniger MA, Pulford K, Gesk S, Ehrlich S, Banham AH, Lyne L, Martin-Subero JI, Siebert R, Dyer MJ, Möller P, Barth TF (October 2006). "Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11A(XL) protein are frequent in primary mediastinal B-cell lymphoma". Leukemia. 20 (10): 1880–2.
  PMID 16871282
  .
• Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns". Genome Biology. 8 (8): R154.
  PMID 17672918
  .

External links

• BCL11A+protein,+human at the U.S. 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 on a gene on human chromosome 2 is a stub. You can help Wikipedia by expanding it.

• v
• t
• e