Regulation of the Chlamydia trachomatis Histone H1-Like Protein Hc2 Is IspE Dependent and IhtA Independent

Abstract

The chlamydial histone-like proteins, Hc1 and Hc2, function as global regulators of chromatin structure and gene expression. Hc1 and Hc2 expression and activity are developmentally regulated. A small metabolite that disrupts Hc1 interaction with DNA also disrupts Hc2 interactions; however, the small regulatory RNA that inhibits Hc1 translation is specific to Hc1.The obligate intracellular bacterium Chlamydia trachomatis is the leading cause of infectious blindness worldwide (19) and the most prevalent bacterial agent of sexually transmitted disease in industrialized and developing countries (20). Chlamydiae undergo a unique biphasic developmental cycle, alternating between two developmental forms. Infection of the host cell is initiated by the metabolically inert elementary body (EB), which possesses a characteristic core of condensed chromatin. Following internalization, the chromatin becomes dispersed, transcription and translation are initiated, and EBs differentiate to the metabolically active reticulate bodies (RBs). RBs replicate for 18 to 48 h within a membrane-bound vacuole called an inclusion until they asynchronously differentiate to EBs, a process characterized by compaction of the chromatin. The EBs are released from the host cell, and a new round of infection begins (9, 15).Two DNA binding proteins, Hc1 and Hc2, are believed to be responsible for the compaction of the chlamydial genome (4,8,12,17). Hc1 and Hc2 (encoded by hctA and hctB, respectively) bear primary amino acid similarity to eukaryotic histone H1 and are expressed late in the developmental cycle concomitantly with RB-to-EB conversion and chromatin condensation (3, 15). Hc1 is conserved among the chlamydiae, while Hc2 displays variable molecular weight depending on the species (7,13,14,16,18). Overexpression of either of these two proteins in Escherichia coli results in compaction of the bacterial chromatin, although the ultrastructure of the DNA-protein complex is distinct (2, 4). In particular, overexpression of Hc1 in E. coli causes chromatin condensation ultrastructurally similar in appearance to the spherical condensed nucleoids of EBs (2), while overexpression of Hc2 induces a condensed nucleoid with a more toroidal appearance. Expression of Hc1 in E. coli leads to a down regulation of transcription, translation, and bacterial replication in conjunction with condensation of the chromatin (1). Hc1 and Hc2 have both been found to strongly repress transcription and translation in vitro by modulating DNA topology and/or binding to DNA and RNA (1, 10, 11).The observed effects on chromatin structure and activity in E. coli are believed to reflect the native function of the histones in chlamydiae as they are considered to act as global regulators of chlamydial gene expression during the terminal differentiation of RBs to EBs at the end of the developmental cycle. Expression of the chlamydial histones in E. coli is effectively lethal, as E. coli apparently lacks the ability to release its chromatin from the constraints imposed by Hc1 or Hc...

Identification of the Base-Pairing Requirements for Repression of hctA Translation by the Small RNA IhtA Leads to the Discovery of a New mRNA Target in Chlamydia trachomatis

“…7B, compare panel C to D). Co-transformation with hctBcheZ and wt ihtA served as an additional control as we have previously shown that IhtA does not repress hctB expression [27]. As anticipated, IhtA did not repress expression of the HctBCheZ fusion protein as evidenced by gain of full motility (Fig.…”

1-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (IDS) is encoded by multicopy genes in gymnosperms Ginkgo biloba and Pinus taeda

“…For example, hexokinase1, a catalytic enzyme, could relay the glucose signal to the gene expression by entering the nucleus (Rolland et al 2006). It is also interesting to note that MEcPP, the upstream metabolite of HMBPP, was shown to cause the disruption of the chlamydial histone-DNA interactions (Grieshaber et al 2006). These rather unusual possibilities on the roles of a GbIDS isozyme and its substrate in the transcription regulation must be supported by further experiments.…”

Reconsidering the nature and mode of action of metabolite retrograde signals from the chloroplast

“…Interestingly, oxidative stress in bacterial cultures induced MEcPP production (Ostrovsky et al, 1998) and MEcPP has been involved with the disruption of the interaction between chlamydial histone-like proteins and DNA. This would suggest that MEcPP could affect chromatin remodeling and gene expression (Grieshaber et al, 2006). However, direct evidence for MEcPP movement and its mechanism of action in plants is still lacking and deserves further investigation.…”