COMPARATIVE AND FUNCTIONAL-ANALYSIS OF THE AP2 PROMOTER INDICATES THAT CONSERVED OCTAMER AND INITIATOR ELEMENTS ARE CRITICAL FOR ACTIVITY

AP-2 is a developmentally-regulated transcription factor expressed in ectodermal cell lineages, The AP-2 protein is essential for neural tub e, craniofacial and body wall morphogenesis and has been implicated in oncogenesis, Here we report the isolation of the AP-2 promoter from h uman, mouse and chicken, The initiation sites for the human gene have been mapped in a variety of cell lines, including several derived from breast tumours, Initiation occurs just upstream of an IR3-like repeti tive element, present in the human and mouse genes, but absent in chic ken, The cis-acting elements responsible for promoter activity in huma n HeLa cells have been mapped both in vivo and in vitro, The proximal promoter contains binding sites for transcription factors AP-2, NF-1 a nd octamer proteins, but lacks a TATA box motif, Functional analysis d emonstrates that the octamer binding site is the critical component of basal promoter activity, In addition, the promoter relies on an initi ator element for efficient start site utilization, There is an excelle nt correlation between the requirement for the initiator and octamer e lements in transcription assays and the conservation of these cis-acti ng sequences between chicken, mouse and human.