YY1 AND SP1 TRANSCRIPTION FACTORS BIND THE HUMAN TRANSFERRIN GENE IN AN AGE-RELATED MANNER

The iron-binding protein transferrin has major roles in transporting, delivering, and sequestering ferric ions acquired by body tissues. Yet , during aging, serum transferrin levels decrease in humans. Likewise, in transgenic mice carrying chimeric human transferrin transgenes, li ver expression of transferrin transgenes decreases with age. The aging regulation is due to decreased gene transcription. Electrophoretic mo bility shift assays and antibody-recognition have revealed the binding of 5' regulatory elements of the human transferrin gene by three YY1 proteins, called YY1, YY1-a, and YY1-b, and an Sp1-a transcription fac tor. An age-related increase in YY1-a and YY1-b binding activities and a decrease in Sp1-like binding activity were shown. Since Sp1 is a po sitive transcription factor and YY1 can be a negative transcription fa ctor, the alterations in their binding with age could cause the decrea sed transcription of the human transferrin transgene, and also the age -related decreased serum transferrin levels in humans.