Rey Carabeo, PhD



BS, University of California, Los Angeles
PhD, University of Wisconsin-Madison
Postdoctoral training, Rocky Mountain Laboratory, NIAID


We are elucidating mechanisms of iron-dependent regulation of gene expression in Chlamydia. We identified an iron-dependent transcriptional repressor (YtgR) that exists as a fusion with an ABC transporter subunit (YtgC). This fusion protein precursor is cleaved to liberate the repressor domain. To determine gene targets of YtgR, we are utilizing a combination of transcriptomics of iron-starved chlamydiae and chromatin immunoprecipitation and sequencing (ChIP-seq) approach. A surprising finding is the YtgR regulation of transcription of the trp operon, specifically the open reading frames trpB and trpA from an alternative promoter. In this context, we determined that YtgR acts as a tryptophan-dependent trans-attenuator towards trpBA expression, possibly as part of the bacteria’s efforts in maintaining a fine-tuned trp operon expression in the absence of a discernible TrpL or TRAP-dependent attenuation mechanisms.

Finally, we extend our initial characterization of YtgR to include additional levels of regulation of its function. Like other iron-dependent transcriptional repressor, it requires iron for homodimerization and DNA binding. However, recent findings indicate that it is also regulated translationally and by proteolytic cleavage. The former involves a rare triple tryptophan motif that renders its translation sensitive to tryptophan levels, and this aspect of YtgR is related to its role as a trans-attenuator described above. Cleavage of the precursor protein liberates the YtgR repressor domain. We are currently investigating the identity of the protease(s) involved, the cleavage site, and the significance of this regulation on YtgR function and the chlamydial response to iron starvation.