Myc and YY1 mediate activation of the Surf-1 promoter in response to serumgrowth factors

The human Surf-1 and Surf-2 genes are divergently transcribed and share a s ingle bi-directional promoter. The addition of serum growth factors to seru m-starved cells activates transcription in the Surf-1 direction, but has no effect on transcription in the Surf-2 direction. Mutations that block the binding of Wi to a site immediately downstream of the major Surf-1 transcri ption start point abolish this response to serum factors. Here we show that over-expression of mitogen-activated protein (MAP) kinase phosphatase MKP- 1, an inhibitor of the MAP kinase cascade, also blocks the response the Sur f-1 promoter to serum factors. YY1 has previously been shown to interact wi th several transcription factors including Myc. We show that although the S urf-1/Surf-2 promoter does not contain Myc binding sites (E-boxes), Myc ove r-expression, or the activation of a Myc-oestrogen receptor fusion protein, activates transcription in the Surf-1 direction and that this response to Myc requires a functional YY1 binding site. Our data suggest that the MAP k inase cascade is required for the stimulation of Surf-1 promoter activity a nd that the Myc-YY1 interaction mediates this response. (C) 2000 Elsevier S cience B.V. All rights reserved.