Pituitary Homeobox Protein 1

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Function

As a homeodomain protein is plays a key role in developing adult organisms. It is a transcription factor that leads to the activation of gene promoters and allows them to execute transcription. PITX1, along with the other homeodomain proteins, have a specific DNA binding. It evidently resides in the nucleus, and as a transcription factor it binds to DNA and is sequence-specific in its binding. As a transcription factor it can promote or enhance specific genes and has an effect on RNA polymerase II. It regulates the mRNA produced by the PITX1 gene as well. It activates the transcription of a variety of pituitary genes.

The PITX1 protein and the PITX2 protein are each some of the first transcription factors that are in pituitary glands. They are bicoid proteins as they can affect the maternal gene and then have effects on fetal development. The two transcription factors are first in progenitor cells as Rathke’s pouch is being formed. PITX1 can increase the expression of some genes. In mice it had been studied that if mice had completely lost all their PITX1 proteins then there would be some cells in the pituitary that are much more prevalent than others and some that completely lose prevalence in the pituitary. This proves how the PITX1 protein has a vital role in balancing the pituitary. It was found in 1999, to be important for gonadotropes and their transcription. PITX1 is most common in a specific pituitary cell and this type of cell includes genes that are in glycoprotein hormone subunit alpha as well as luteinizing hormone beta. How PITX1 interacts with cell-restricting factors is what makes its interactions so specific. It interacts with many cell-restricting factors which gives it the ability to activate prolactin and growth hormones. In corticotrope cells it interacts with basic helix-loop-helix heterodimer to activate the pro-opiomelancortin promoter. This all further proves how PITX1 is intricate in how it interacts with other molecules to act as a transcription factor.

Disease

Stickleback Fish

The effects of the PITX1 protein have been studied further within stickleback fish. The researchers studied two isolated populations of fish. They theorized how the PITX1 gene and how it encodes the protein acts a “regulatory switch”. However, defects in the switch can lead to defects in the development of the hind limbs. In marine stickleback fish they have a pelvis and a protective spine. But, in the freshwater populations of stickleback fish they physically show deformities in these body parts. The freshwater stickleback fish have a missing pelvis, or it is at least reduced and less prevalent. This has been found to be due to the PITX1 gene not properly encoding the PITX1 protein, which is ever so important in the development of the hind limbs of animals. Using the stickleback fish, researchers further identified how the PITX1 gene and protein are regulated differently depending on the tissue types in the animal. Therefore, the jaw tissue, pituitary tissue and the pelvic tissue are all regulated differently for PITX1. This is how it was found that the PITX1 for pelvic tissue has a regulatory switch in marine stickleback fish, but does not have a regulatory switch for pelvic tissue in freshwater stickleback fish. The reason for the lack of a pelvic regulatory switch in freshwater stickleback fish is due to the mutation or deletion that gets in the way of a pelvic promoter (Pel-beta) and its general function.

Structural highlights

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