Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032.
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032;
Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18701-18710. doi: 10.1073/pnas.2005726117. Epub 2020 Jul 20.
Yin Yang 1 (YY1) is a DNA-binding transcription factor that either activates or represses gene expression. YY1 has previously been implicated in the transcriptional silencing of many retroviruses by binding to DNA sequences in the U3 region of the viral long terminal repeat (LTR). We here show that YY1 overexpression leads to profound activation, rather than repression, of human T lymphotropic virus type 1 (HTLV-1) expression, while YY1 down-regulation reduces HTLV-1 expression. The YY1 responsive element mapped not to YY1 DNA-binding sites in the HTLV-1 LTR but to the R region. The HTLV-1 R sequence alone is sufficient to provide YY1 responsiveness to a nonresponsive promoter, but only in the sense orientation and only when included as part of the mRNA. YY1 binds to the R region of HTLV-1 RNA in vitro and in vivo, leading to increased transcription initiation and elongation. The findings indicate that YY1 is a potent transactivator of HTLV-1 gene expression acting via binding viral RNA, rather than DNA.
阴阳 1 (YY1) 是一种 DNA 结合转录因子，可激活或抑制基因表达。YY1 先前已被牵涉到通过与病毒长末端重复 (LTR) 的 U3 区域中的 DNA 序列结合而使许多逆转录病毒的转录沉默。我们在此表明，YY1 的过表达导致人 T 淋巴细胞病毒 1 (HTLV-1) 的表达的显著激活，而不是抑制，而 YY1 的下调则降低 HTLV-1 的表达。YY1 反应元件不是映射到 HTLV-1 LTR 中的 YY1 DNA 结合位点，而是映射到 R 区。HTLV-1 R 序列本身足以提供对非反应性启动子的 YY1 反应性，但仅在正向且仅当包含在 mRNA 的一部分时。YY1 在体外和体内与 HTLV-1 RNA 结合，导致转录起始和延伸增加。这些发现表明，YY1 通过结合病毒 RNA 而不是 DNA，是 HTLV-1 基因表达的有效转录激活剂。
