Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency

Figure 1

Regulation of HIV transcription initiation and elongation. (a) HIV LTR organization. This only represents a small subset of cis-elements and transcription factors, which bind these sites. (b) Cellular transcription factors are recruited to LTR elements and initiation complex forms at the transcriptional start site. Nucleosomes are posttranslationally modified favoring a condensed chromatin structure that impedes RNAP II transcriptional elongation. (c) RNAP II processes a short distance downstream from the transcriptional start site when DSIF and NELF induce a pause in transcription. Pcf11 reinforces this block in elongation by prematurely terminating the transcription of the short nascent RNA product. HDAC recruitment to the paused complex reinforces a transcriptionally repressed chromatin state. The red asterisk depicts phosphorylation of RNAP II CTD at serine 5 position. (d) RNAP II elongation complex is released from the transcriptional pause by the recruitment of P-TEFb, which mediates hyperphosphorylation of the CTD at serine 2 position and phosphorylation of DSIF, which induces NELF disassociation from the complex (red asterisks indicate key phosphorylation events). The recruitment of chromatin remodeling machinery such as HATs and PBAF SWI/SNF facilitates acetylation of nucleosomes, which displaces the blocking nucleosome and supports transcription elongation.