- 作者: Wei Gu; Qi Huang; Gary S. Hayward
- 作者服務機構: Departments of; a Pharmacology and Molecular Sciences and; b Oncology; The Molecular Virology Laboratories, Johns Hopkins University School of; Medicine, Baltimore, Md., USA
- 中文摘要: --
- 英文摘要: Expression of the IE110 (ICP0) transactivator protein of HSV appears to be critical for reactivation from the latent state and occurs at immediate-early times during the lytic cycle under the control of an upstream divergent enhancer-promoter region that contains multiple Oct and Sp-1 binding sites overlapping with VP16 response elements. Surprisingly, the large 800-bp first intron of the HSV-1 IE 110 gene also proved to have a complex repetitive orga- nization encompassing multiple transcription factor binding sites within four distinct domains. DNase I footprinting studies revealed that 13 of 17 copies of a 15-bp repeated element represented high-affinity binding sites for the cellu- lar YY 1 repressor protein. Between 4 and 7 of these sites are direct tandem repeats and the rest are interspersed with three repeated AT-rich motifs and a dyad symmetry region containing two strong AP-1 binding sites and an adja- cent SP-1 binding site on each arm. Several of the YY 1 sites also bound weakly to SRF. The intron also contains four clustered purine/pyrimidine tracts of between 16 and 23 bp long. Both the AP-1/AP-2/SP-1 dyad protein binding region and, to a lesser extent, the YY1 tandem-repeat cluster conferred responsiveness to TPA when placed upstream of a heterologous promoter in transient expression assays. The functional significance of the HSV-1 IE110 intron region is unknown as yet, but the novel arrangement of tandemly repeated YY1 sites has the potential to produce structural bending and tran- scriptional attenuation effects. Interestingly, few of these transcription factor binding motifs are conserved in the equivalent IE110 intron of HSV-2, and the domain appears to represent a unique alternative control region that is specific for HSV-1.
- 中文關鍵字: --
- 英文關鍵字: Transcription factor binding sites; DNaseI footprinting; TPA response elements; Type-specific control region