GATA1

Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a is_associated_with::protein that in humans is encoded by the GATA1 is_associated_with::gene.

GATA-1 is a member of the is_associated_with::GATA transcription factor family and is involved in is_associated_with::cell growth and is_associated_with::cancer. This protein plays a role in erythroid development by regulating the switch of fetal is_associated_with::hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and is_associated_with::thrombocytopenia.

Function
GATA1 is required for the maturation of is_associated_with::red blood cells, is_associated_with::megakaryocytes, is_associated_with::mast cells and is_associated_with::eosinophils. GATA1 mutant mice die in early embryonic development due to inability to form mature erythroid cells. GATA1 mutation in humans causes congenital anemias and thrombocytopenias.

GATA1 was first described as a is_associated_with::red blood cell lineage transcription factor that activates the is_associated_with::beta-globin gene. During red blood cell maturation, GATA1 activates nearly all erythroid-specific genes while silencing genes associated with the immature proliferative red blood cell precursor cells (erythroblasts). Initial genome-wide studies found that GATA1 activated and repressed similar numbers of genes. These studies examined gene expression changes in relation to total RNA content, a standard called into question by the dramatic changes in cell size and morphology that accompany erythroblast maturation. More recent work suggests that GATA1 strongly activates a small number of genes while, either directly or indirectly, repressing most of the genome as erythroblasts undergo the final stages of their terminal maturation.

GATA-1 has been found to enhance the transcription rates of the α-is_associated_with::spectrin gene by up to 100 fold in humans.

Structure
The molecule contains three domains: the C-finger, the N-finger, and the Activation Domain. The C-finger, named for being near the is_associated_with::C-terminal, has a is_associated_with::Zinc finger DNA binding domain. The N-finger, named for being near the is_associated_with::N-terminal also binds DNA and a cofactor named FOG1 (friend of GATA). The Activation Domain is responsible for GATA1's strong transcriptional activation. The gene for GATA1 is on the X-chromosome.

Disease linkage
Mutations in GATA1 cause anemias and thrombocytopenia in human patients. Disease-causing GATA1 mutations are present in the zinc finger DNA binding domains as well as protein-protein interaction domains of GATA1.

Mutations in exon 2 of the GATA1 gene are present in almost all cases of is_associated_with::Down syndrome (DS)-associated is_associated_with::acute megakaryoblastic leukemia (AMKL). While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).

The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop. The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL. This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.

Increased levels of GATA1 expression have been found in individuals with is_associated_with::major depressive disorder. Expression of GATA1 in the prefrontal cortex results in a decrease of the expression of synapse-related genes, a loss of dendritic spines and dendrites, and can produce depressive behavior in rat models of depression.

Interactions
GATA1 has been shown to interact with: • 2