Intrinsic DNA curvature in trypanosomes

Area of Science:

• Molecular Biology
• Genetics
• Parasitology

Background:

• Trypanosoma cruzi and Trypanosoma brucei cause Chagas disease and African sleeping sickness, respectively.
• Canonical RNA polymerase II promoter signals are absent in these parasites.
• DNA secondary structure, including curvature, is implicated in biological processes and transcription initiation.

Purpose of the Study:

• To investigate the genome-wide distribution of intrinsic DNA curvature in T. cruzi and T. brucei.
• To determine if DNA curvature serves as a regulatory signal in trypanosomatids.

Main Methods:

• Developed and utilized a region integrated intrinsic curvature (RIIC) scoring method.
• Performed a genome-wide search for sequence-dependent DNA curvature.
• Correlated RIIC scores with known transcription start sites and regulatory regions.

Main Results:

• A non-random distribution of sequence-dependent DNA curvature was observed in both species.
• High RIIC scores correlated with transcription start sites in T. cruzi.
• In T. brucei, high RIIC scores were associated with RNA polymerase II initiation and termination sites, as well as subtelomeric regions containing VSG genes.

Conclusions:

• A link exists between DNA conformational signals and gene expression in T. cruzi and T. brucei.
• Sequence-dependent DNA curvature is associated with transcriptional regulatory regions.
• Intrinsic DNA curvature is present in subtelomeric regions of T. brucei chromosomes involved in immune evasion.