Functional Analysis of the Promoter Region of the Gene Encoding Chicken Calbindin D28K

Abstract

Vitamin D controls the expression of many genes, among which are those encoding osteocalcin (Price and Baukol, 1980), collagen type I (Kream et al., 1986), matrix Gla protein (Fraser et al., 1988), parathyroid hormone (Okazaki et al., 1988), c myc (Simpson et al., 1987), and a family of calcium-binding proteins termed calbindins. At least two types of calbindins exist: a M 9,000 protein (Calbindin D9K), present in mammalian intestine (Kallfelz et al., 1967), placenta (Bruns et al., 1978), yolk sac (Bruns et al., 1986), and a larger M_r 28,000 protein (calbindin D28K) identified in avian intestine (Wasserman and Taylor, 1966) and many other tissues (Christakos and Norman, 1980). Subsequent studies have shown that mam malian kidney (Pansini et al., 1984), brain (Jande et al., 1981) and other tissues (Norman et al., 1982) also express a M_r 28,000 protein which is immunologically similar but not identical to the avian Calbindin D28K. 1,25 dihydroxycholecalciferol [1,25(OH)₂D₃], the hormonally active form of vitamin D, has been shown to regulate the levels of avian intestinal calbindin D28K from undetectable in vitamin D deficient chickens, to up to 13% of the cytoplasmic protein of the intestinal cell (Christakos et al., 1979). This hormonal induction by 1,25(OH)2D3 is mediated through a high affinity soluble receptor protein (Pike et al., 1987) in a manner analogous to other steroid hormone systems. It is therefore hypothesized that following hormone receptor binding, this complex interacts with a cis acting element in the promoter region of the calbindin D28K gene and regulates transcription of the corresponding mRNA.