B-cell lymphoma/leukemia 11A is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''BCL11A''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
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.
The protein associates with the
SWI/SNF complex, that regulates gene expression via chromatin remodeling.
''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
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
transition.
Furthermore, BCL11A is expressed in the brain, where it forms a protein complex with CASK to regulate axon outgrowth and branching.
In the
neocortex, BCL11A binds to the ''TBR1'' regulatory region and inhibits the expression of ''TBR1''.
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
Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cl ...
and
sickle cell anemia
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
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
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
.
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.
Interactions
BCL11A has been shown to interact with a number of proteins. BCL11A was initially discovered as a
COUP-TFI interacting protein. In the nucleus, BCL11A forms paraspeckles that co-localize with
NONO
Nono may refer to:
Places
* Nono, Argentina, a municipality in the Province of Córdoba
* Nono, Ecuador, a parish in the municipality of Quito in the province of Pichincha
* Nono, Illubabor, Oromia (woreda), Ethiopia, or Nono Sele
** Nono, Illub ...
.
In neurons, BCL11A interacts with
CASK
A barrel or cask is a hollow cylindrical container with a bulging center, longer than it is wide. They are traditionally made of wooden staves and bound by wooden or metal hoops. The word vat is often used for large containers for liquids, u ...
to regulate target genes.
Furthermore, BCL11A interacts with the neuron-specific protein
TBR1
T-box, brain, 1 is a transcription factor protein important in vertebrate embryo development. It is encoded by the ''TBR1'' gene. This gene is also known by several other names: ''T-Brain 1'', ''TBR-1'', ''TES-56'', and ''MGC141978''. TBR1 is ...
, which is also implicated in intellectual disability and autism spectrum disorder.
References
Further reading
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External links
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Transcription factors
{{gene-2-stub