Abstract

Studies on the regulation of phage Ø29 gene expression revealed a new mechanism to accomplish simultaneous activation and repression of transcription leading to orderly gene expression. Two phage-encoded early proteins, p4 and p6, bind synergistically to DNA, modifying the topology of the sequences encompassing early promoters A2c and A2b and late promoter A3 in a hairpin that allows the switch from early to late transcription. Protein p6 is a nucleoid-like protein that binds DNA in a non-sequence specific manner. Protein p4 is a sequence-specific DNA binding protein with multifaceted sequence-readout properties. The protein recognizes the chemical signature of only one DNA base on the inverted repeat of its target sequence through a direct-readout mechanism. In addition, p4 specific binding depends on the recognition of three A-tracts by indirect-readout mechanisms. The biological importance of those three A-tracts resides in their individual properties rather than in the global curvature that they may induce.

Highlights

  • Viral genes are expressed in a time-dependent manner for optimization of protein function

  • The founding member of “anti-σ factors” is the AsiA protein of bacteriophage T4, which inhibits transcription from bacterial promoters and phage early promoters, and co-activates transcription from phage middle promoters [2,3,4]

  • The switch from early to late transcription of the Ø29 genome is tightly regulated to ensure the appropriate sequence of gene expression

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Summary

Introduction

Viral genes are expressed in a time-dependent manner for optimization of protein function. Transcription factors are mostly regulatory proteins that bind to DNA sequences generally at or nearby the promoter sequence These sequence-specific protein interactions are usually responsible for regulating transcription initiation [6]. Bacteria do not have nucleosomes, they do have nucleoid proteins such as Fis or H-NS, which organize the genomes and bend DNA upon binding Both proteins regulate transcription by affecting the DNA structure as well as antagonizing the function of other transcription factors, mainly acting as repressors [7,8,9]. P6 cooperates with p4 in transcription regulation [54] Both proteins bind synergistically to the sequence containing early promoters A2c, A2b and late promoter. A3 resulting in a multimeric complex that elicits the switch from early to late transcription by repressing early promoters A2c and A2b and simultaneously activating late promoter A3 [55]

Protein p4-DNA Complex
Zipper Model for p4 Specific Sequence Recognition and DNA Binding
Regulation of the Switch from Early to Late Gene Expression
Conclusions
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