HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells

eLife

Youn-Tae Kwak¹  Jonathan E Reeder²  Iván D'Orso³  Ryan P McNamara⁴  Christian V Forst⁴ 

[1] Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States;Department of Biological Sciences, University of Texas at Dallas, Richardson, United States;Department of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, United States;Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States;

关键词: transcription factor;    chromatin;    RNA polymerase II;    epigenetic;    transcription;   

DOI  :  10.7554/eLife.08955

来源: DOAJ

【 摘 要 】

HIV encodes Tat, a small protein that facilitates viral transcription by binding an RNA structure (trans-activating RNA [TAR]) formed on nascent viral pre-messenger RNAs. Besides this well-characterized mechanism, Tat appears to modulate cellular transcription, but the target genes and molecular mechanisms remain poorly understood. We report here that Tat uses unexpected regulatory mechanisms to reprogram target immune cells to promote viral replication and rewire pathways beneficial for the virus. Tat functions through master transcriptional regulators bound at promoters and enhancers, rather than through cellular ‘TAR-like’ motifs, to both activate and repress gene sets sharing common functional annotations. Despite the complexity of transcriptional regulatory mechanisms in the cell, Tat precisely controls RNA polymerase II recruitment and pause release to fine-tune the initiation and elongation steps in target genes. We propose that a virus with a limited coding capacity has optimized its genome by evolving a small but ‘multitasking’ protein to simultaneously control viral and cellular transcription.

【 授权许可】

Unknown