Histone acetylations mark origins of polycistronic transcription in Leishmania major

The chromosomal location of TATA-binding protein (TBP or TRF4), Small Nuclear Activating Protein complex (SNAP50), and H3 histones were assessed in Leishmania major using microarrays hybridized with DNA obtained through chromatin immunoprecipitation (ChIP-chip). The TBP and SNAP50 binding patterns were almost identical and high intensity peaks were associated with tRNAs and snRNAs. Only 184 peaks of acetylated H3 histone were found in the entire genome, with substantially higher intensity in rapidly-dividing cells than stationary-phase. The majority of the acetylated H3 peaks were found at divergent strand-switch regions, but some occurred at chromosome ends and within polycistronic gene clusters. Almost all these peaks were associated with lower intensity peaks of TBP/SNAP50 binding a few kilobases upstream, evidence that they represent transcription initiation sites.The first genome-wide maps of DNA-binding protein occupancy in a kinetoplastid organism suggest that H3 histones at the origins of polycistronic transcription of protein-coding genes are acetylated. Global regulation of transcription initiation may be achieved by modifying the acetylation state of these origins.Kinetoplastids are early-branching protists with unusual mechanisms of gene expression. While some are harmless free-living organisms, other members of this group infect a range of plants and animals, causing significant human disease in the form of African Sleeping Sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania major), which kill approximately 400,000 people per year. The parasites are transmitted to their preferred hosts by different insect vectors where they reside and replicate as host-adapted and vector-adapted forms, respectively, with remarkably different morphologies.Leishmania are transmitted by the bite of a sand fly, where they dwell in the mid-gut as promastigotes. The parasites make their way to the salivary glands where they undergo