FOXP1

Forkhead box protein P1 is a is_associated_with::protein that in humans is encoded by the FOXP1 is_associated_with::gene. FOXP1 is necessary for the proper development of the brain, heart, and lung in is_associated_with::mammals. It is a member of the large FOX family of is_associated_with::transcription factors.

Function
This gene belongs to subfamily P of the is_associated_with::forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a is_associated_with::tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms.

Foxp1 is a transcription factor; specifically it is a transcriptional is_associated_with::repressor. Fox genes are part of a forkhead DNA-binding domain family. This domain binds to sequences in promoters and enhancers of many genes. Foxp1 regulates a variety of important aspects of development including tissue development of: the lungs, brain, thymus and heart. In the heart Foxp1 has 3 vital roles, these include the regulation of cardiac is_associated_with::myocyte maturation and proliferation, outflow tract separation of the is_associated_with::pulmonary artery and is_associated_with::aorta, and expression of Sox4 in cushions and myocardium. Foxp1 is also an important gene in muscle development of the esophagus and esophageal epithelium. Foxp1 is also an important regulator of lung airway morphogenesis. Foxp1 knockout embryos display severe defects in cardiac is_associated_with::morphogenesis. A few of these defects include is_associated_with::myocyte maturation and proliferation defects that cause a thin ventricular myocardial compact zone, non-separation of the is_associated_with::pulmonary artery and is_associated_with::aorta, and is_associated_with::cardiomyocyte proliferation increase and defective differentiation. These defects, caused by Foxp1 inactivation, lead to fetal death. Disruptions of FoxP1 have been identified in very rare human patients and – similarly to FoxP2 - lead to cognitive dysfunction, including intellectual disability and is_associated_with::autism spectrum disorder, together with language impairment.

It was shown that the is_associated_with::embryonic stem cell (ESC)-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for is_associated_with::pluripotency, including is_associated_with::OCT4, NANOG, is_associated_with::NR5A2, and is_associated_with::GDF3, while concomitantly repressing genes required for ESC differentiation. This isoform also promotes the maintenance of ESC pluripotency and contributes to efficient reprogramming of somatic cells into is_associated_with::induced pluripotent stem cells. These results reveal a pivotal role for an Alternative splicing event in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.

The expression of FOXP1 was also implicated in the biology of B cell malignancies, and is regulated by is_associated_with::non-coding RNA (miRNA) termed is_associated_with::miR-150.