CLONING OF AN SNF2 SWI2-RELATED PROTEIN THAT BINDS SPECIFICALLY TO THE SPH MOTIFS OF THE SV40 ENHANCER AND TO THE HIV-1 PROMOTER/

We have isolated a human cDNA clone encoding HIP116, a protein that bi nds to the SPH repeats of the SV40 enhancer and to the TATA/initiator region of the human immunodeficiency virus (HIV)-1 promoter. The predi cted HIP116 protein is related to the yeast SNF2/SW12 transcription fa ctor and to other members of this extended family and contains seven d omains similar to those found in the vaccinia NTP1 ATPase. Interesting ly, HIP116 also contains a C3HC4 zinc-binding motif (RING: finger) int erspersed between the ATPase motifs in an arrangement similar to that found in the yeast RADS and RAD16 proteins. The HIP116 amino terminus is unique among the members of this family, and houses a specific DNA- binding domain, Antiserum raised against HIP116 recognizes a 116-kDa n uclear protein in Western blots and specifically supershifts SV40 and HIV-1 protein-DNA complexes in gel shift experiments. The binding site for HIP116 on the SV40 enhancer directly overlaps the site for TEF-1, and like TEF-1, binding of HIP116 to the SV40 enhancer is destroyed b y mutations that inhibit SPH enhancer activity in vivo. Purified fract ions of HIP116 display strong ATPase activity that is preferentially s timulated by SPH DNA and can be inhibited specifically by antibodies t o HIP116. These findings suggest that HIP116 might affect transcriptio n, directly or indirectly, by acting as a DNA binding site-specific AT Pase.