Transcription factor GATA-6, also known as GATA-binding factor 6 (GATA6), is
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 ''GATA6''
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 ...
.
The gene product preferentially binds (A/T/C)GAT(A/T)(A) of the
consensus binding sequence.
Clinical significance
Mutations in the gene have been linked with pancreatic
agenesis In medicine, agenesis () refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue. Many forms of agenesis are referred to by individual names, depending on the organ affected:
* A ...
and
congenital heart defect
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascul ...
s.
Lung Endodermal Epithelial Development
GATA-6, a
zinc finger transcription factor
Zinc finger transcription factors or ZF-TFs, are transcription factors composed of a zinc finger- binding domain and any of a variety of transcription-factor effector-domains that exert their modulatory effect in the vicinity of any sequence to wh ...
, is important in the
endodermal differentiation of organ tissues.
It is also indicated in proper lung development by controlling the late differentiation stages of alveolar epithelium and aquaporin-5 promoter activation. Furthermore, GATA-6 has been linked to the production of LIF, a cytokine that encourages proliferation of endodermal embryonic stem cells and blocks early epiblast differentiation. If left unregulated in the developing embryo, this cytokine production and chemical signal contributes to the phenotypes discussed further below.
Upon the disruption of GATA-6 in an embryo, the distal lung epithelial development is stunted in transgenic mice models
The
progenitor cell
A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only differ ...
s, or stem cells, for alveolar epithelial tissues develop and are specified appropriately, however further differentiation does not occur. Also the distal-proximal bronchiole development is affected, resulting in a reduced quantity of airway exchange sites.
This branching deficit, which will cause bilateral
pulmonary hypoplasia
Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that int ...
after birth, has been locally associated with areas lacking differentiated alveolar epithelium, implicating this phenotype as inherent to endodermal function, and thus may be indirectly linked to improper GATA-6 expression.
That is, a deficit of bronchiole branching may not be a result of direct transcriptional error in GATA-6, but rather a side effect of such an error.
See also
*
GATA transcription factor
GATA transcription factors are a family of transcription factors characterized by their ability to bind to the DNA sequence "GATA".
GATA transcription factors have been correlated to their broader influence on stem cell development. Findings ho ...
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
External links
*
{{DEFAULTSORT:Gata6
Transcription factors