YY1 and Spl Transcription Factors Bind the Human Transferrin Gene in an Age-Related Manner

Abstract

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, liver expression of transferrin transgenes decreases with age. The aging regulation is due to decreased gene transcription. Electrophoretic mobility 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 factor. 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 positive transcription factor and YY1 can be a negative transcription factor, the alterations in their binding with age could cause the decreased transcription of the human transferrin transgene, and also the age-related decreased serum transferrin levels in humans.

Betulinic Acid Induces Apoptosis in Humam Mucoepidermoid Carcinoma Cells Through Regulating Specificity Protein 1 and Its Downstream Molecule, Survivin

“…Inhibition of Sp1 expression has been shown to down-regulate tumor cell growth as well as tumor initiation in athymic mice 24,[26][27][28] . The importance of Sp 1 as a drug target is due not only to its overexpression in several tumor types but also to its relatively low expression in normal human tissues, and this is consistent with studies that reported the decrease of Sp1 expression in increasing age 29,30) . Therefore, we inferred that Sp1 can be a potential molecular target for MEC treatment.…”

Transcription Factors Sp1 and Hif2α Mediate Induction of the Copper-transporting ATPase (Atp7a) Gene in Intestinal Epithelial Cells during Hypoxia

“…Few studies to date have investigated Sp1-like factors in the regulation of iron homeostasis-related genes. One recent study suggested that the age-related decline in hepatic transferrin gene expression may relate in part to Sp1-like DNA binding activity (28). The hepatic Hfe gene, which is mutated in some types of hereditary hemochromatosis in humans, also has apparent Sp1-like binding sites (29).…”

Molecular analysis of Ceruloplasmin in a South African cohort presenting with oesophageal cancer

“…YY1 is a zinc finger protein that has been shown to play a role in iron metabolism, particularly by interacting with transferring. 43 It has also been implicated in gene silencing in the liver. 43 CP is known to interact with transferrin during the transfer of iron molecules across the basolateral membrane of the enterocyte.…”

“…43 It has also been implicated in gene silencing in the liver. 43 CP is known to interact with transferrin during the transfer of iron molecules across the basolateral membrane of the enterocyte. This TF could be involved in simultaneously mediating expression of these two proteins.…”