Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean.

ABSTRACT: Fundamental to biological decision-making is the ability to generate bimodal expression patterns where 2 alternate expression states simultaneously exist. Here, we use a combination of single-cell analysis and mathematical modeling to examine the sources of bimodality in the transcriptional program controlling HIV's fate decision between active replication and viral latency. We find that the HIV transactivator of transcription (Tat) protein manipulates the intrinsic toggling of HIV's promoter, the long terminal repeat (LTR), to generate bimodal ON-OFF expression and that transcriptional positive feedback from Tat shifts and expands the regime of LTR bimodality. This result holds for both minimal synthetic viral circuits and full-length virus. Strikingly, computational analysis indicates th

SUBMITTER: Razooky BS 

PROVIDER: S-EPMC5646755 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature