SATB2
Encyclopedia
Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein
that in humans is encoded by the SATB2 gene
. SATB2 is a DNA-binding protein
that specifically binds nuclear matrix
attachment regions and is involved in transcriptional regulation
and chromatin remodeling
.. SATB2 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.
and environmental factors contribute to the etiology. Current research suggests that several genes are likely to control risk, as well as environmental factors such as maternal smoking.
Re-sequencing studies to identify specific mutations suggest several different genes may control risk to oral clefts, and many distinct variants or mutations in apparently causal genes have been found reflecting a high degree of allelic heterogeneity. Although most of these mutations are extremely rare and often show incomplete penetrance (i.e., an unaVected parent or other relative may also carry the mutation), combined they may account for up to 5% of non-syndromic oral cleft.
SATB2 also likely influences brain development. This is consistent with mouse studies that show SATB2 is necessary for proper establishment of cortical neuron connections across the corpus callosum, despite the apparently normal corpus callosum in heterozygous knockout mice.
(amino acid 352–437 and 482–560) and a classical homeodomain (amino acid 614–677). There is an extraordinarily high degree of sequence conservation, with only three predicted amino-acid substitutions in the 733 residue protein with I481V, A590T and I730T being amino acid differences between the human and the mouse protein.
.
The role of SATB2 in tooth and jaw development is supported by the identification of a de novo SATB2 mutation in a male with profound mental retardation and jaw and tooth abnormalities and a translocation interrupting SATB2 in an individual with Robin sequence. In addition, mouse models have demonstrated haploinsufficiency of SATB2 results in craniofacial defects that phenocopy those caused by 2q32q33 deletion in humans; moreover, full functional loss of SATB2 amplifies these defects.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the SATB2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. SATB2 is a DNA-binding protein
DNA-binding protein
DNA-binding proteins are proteins that are composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that...
that specifically binds nuclear matrix
Nuclear matrix
In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus and is somewhat analogous to the cell cytoskeleton...
attachment regions and is involved in transcriptional regulation
Transcriptional regulation
Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...
and chromatin remodeling
Chromatin remodeling
Chromatin remodeling is the enzyme-assisted movement of nucleosomes on DNA.This is performed by chromatin remodeling complexes like SWI/SNF , RSC and Imitation SWI complexes ....
.. SATB2 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.
Function
With an average worldwide prevalence of 1/800 live births, oral clefts are one of the most common birth defects. Although over 300 malformation syndromes can include an oral cleft, non-syndromic forms represent about 70% of cases with cleft lip with or without palate (CL/P) and roughly 50% of cases with cleft palate (CP) only. Non-syndromic oral clefts are considered ‘complex’ or ‘multifactorial’ in that both genesand environmental factors contribute to the etiology. Current research suggests that several genes are likely to control risk, as well as environmental factors such as maternal smoking.
Re-sequencing studies to identify specific mutations suggest several different genes may control risk to oral clefts, and many distinct variants or mutations in apparently causal genes have been found reflecting a high degree of allelic heterogeneity. Although most of these mutations are extremely rare and often show incomplete penetrance (i.e., an unaVected parent or other relative may also carry the mutation), combined they may account for up to 5% of non-syndromic oral cleft.
SATB2 also likely influences brain development. This is consistent with mouse studies that show SATB2 is necessary for proper establishment of cortical neuron connections across the corpus callosum, despite the apparently normal corpus callosum in heterozygous knockout mice.
Structure
SATB2 is a 733 amino-acid homeodomain-containing human protein with a molecular weight of 82.5 kDa encoded by the SATB2 gene on 2q33. The protein contains two degenerate homeodomain regions known as CUT domainsCUT domain
In molecular biology, the CUT domain is a DNA-binding motif which can bind independently or in cooperation with the homeodomain, which is often found downstream of the CUT domain...
(amino acid 352–437 and 482–560) and a classical homeodomain (amino acid 614–677). There is an extraordinarily high degree of sequence conservation, with only three predicted amino-acid substitutions in the 733 residue protein with I481V, A590T and I730T being amino acid differences between the human and the mouse protein.
Clinical significance
SATB2 was found to be disrupted in two unrelated cases with de novo apparently balanced chromosome translocations associated with cleft palate and Pierre Robin SequencePierre Robin syndrome
Pierre Robin Sequence , also known as Pierre Robin Malformation, is a congenital condition of facial abnormalities in humans. PRS is a sequence: a chain of certain developmental malformations, one entailing the next...
.
The role of SATB2 in tooth and jaw development is supported by the identification of a de novo SATB2 mutation in a male with profound mental retardation and jaw and tooth abnormalities and a translocation interrupting SATB2 in an individual with Robin sequence. In addition, mouse models have demonstrated haploinsufficiency of SATB2 results in craniofacial defects that phenocopy those caused by 2q32q33 deletion in humans; moreover, full functional loss of SATB2 amplifies these defects.