The role of NF-1 factors in regulation of elastin gene transcription.

The -195- to -500-bp region of the human elastin promoter has been shown to convey high activity in neonatal rat aortic smooth muscle cell and pulmonary fibroblast cell cultures. In addition, this region has been implicated in controlling the differential basal level of elastin transcription in these two cell types. The overall goal of this study was to define the positive element(s) within the -195- to - 500-bp region and to identify the trans-acting factors binding to this sequence. A combination of deletion and linker scan mutational analyses localizes the positive element between -401 and -415 bp. Gel shift analyses demonstrate that the positive element binds NF-1 family members. Co-transfection of a CTF1 expression vector in Drosophila Schneider cells shows the ability of an NF-1 family member to activate elastin promoter activity through this site. Comparative Western and Southwestern blot analyses of nuclear extracts isolated from SMC and lung fibroblasts lay the foundation for possible differential regulation of elastin transcriptional levels via cell specific expression of different NF-1 family members.