FOXC1 : forkhead box C1

Description

The FOXC1 (forkhead box C1) is a protein-coding gene located on chromosome 6.

The FOXC1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this action, the FOXC1 protein is called a transcription factor. The FOXC1 protein plays a critical role in early development, particularly in the formation of structures in the front part of the eye (the anterior segment). These structures include the colored part of the eye (the iris), the lens of the eye, and the clear front covering of the eye (the cornea). Studies suggest that the FOXC1 protein may also have functions in the adult eye, such as helping cells respond to oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells. The FOXC1 protein is also involved in the normal development of other parts of the body, including the heart, kidneys, and brain.

FOXC1 is a DNA-binding transcription factor crucial for a wide array of cellular and developmental processes including eye, bones, cardiovascular, kidney, and skin development. It can function as either a transcriptional activator or repressor, binding to the consensus sequence 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' within target gene promoters. Upon DNA binding, FOXC1 induces DNA bending. It acts as a transcriptional coactivator, stimulating Indian hedgehog (Ihh)-induced target gene expression mediated by the transcription factor GLI2, thus regulating endochondral ossification. FOXC1 also serves as a transcriptional coregulator, enhancing the DNA-binding capacity of GLI2 in breast cancer cells. It regulates FOXO1 by binding to a conserved element, 5'-GTAAACAAA-3', in its promoter region, highlighting its role in regulating cell viability and resistance to oxidative stress in the eye. FOXC1 collaborates with transcription factor FOXC2 in regulating genes that maintain podocyte integrity. It inhibits cell growth by halting the cell cycle in the G1 phase through TGFB1-mediated signals. FOXC1 is involved in epithelial-mesenchymal transition (EMT) induction by boosting cell proliferation, migration, and invasion. It participates in chemokine CXCL12-induced endothelial cell migration through the regulation of CXCR4 expression. FOXC1 plays a crucial role in the gene regulatory network essential for epidermal keratinocyte terminal differentiation. It is an essential developmental transcription factor required for mesoderm-derived tissues, such as the somites, skin, bone, and cartilage. FOXC1 positively regulates CXCL12 and stem cell factor expression in bone marrow mesenchymal progenitor cells, contributing to the development and maintenance of mesenchymal niches for hematopoietic stem and progenitor cells (HSPC). It ensures corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner. FOXC1 may function as a tumor suppressor.

FOXC1 is also known as ARA, ASGD3, FKHL7, FREAC-3, FREAC3, IGDA, IHG1, IRID1, RIEG3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing