Identification of thyroid regulatory elements in the Na-K-ATPase alpha 3 gene promoter

A -1027 bp to +108 bp region of Na-K-ATPase alpha (3) gene promoter has bee n searched for the presence of thyroid response elements (TRE). Computer an alysis of this sequence using a consensus TRE sequence revealed the presenc e of four putative TRE rich regions referred to as regions I (-636 to -457 bp), II (-218 to -106 bp), III (-106 to -6 bp) and IV (-6 to +108 bp). Cotr ansfection of the luciferase linked full length construct as well as constr ucts progressively devoid of the TRE rich regions in Cos1 cells revealed th at regions I and III are positively regulated by T-3 whereas there are some sequences in region II which can suppress the positive regulatory effect o f region III but not of region I, TRE IV seems to have no functional role. EMSA of the three functional TRE rich regions (I, II and III) showed strong and specific interaction with thyroid hormone receptor (TR) cloned and exp ressed in baculovirus. The overall results suggest the regulation of Na-K-A TPase alpha (3) gene by T-3 is complex involving several thyroidal regulato ry elements.