Amelie Kraus   email
Research Center for Infectious Diseases

Supervisor:
Prof. Dr. Nicolai Siegel (München)
Promotion Committee:
Prof. Dr. Nicolai Siegel (München)
Dr. Sonja Lorenz (Würzburg)
Prof. Dr. Christian Janzen (Würzburg)
Prof. Dr. Andreas Schlosser (Würzburg)

Identification of factors responsible for the targeted deposition of histone variants in Trypanosoma brucei

During transcription initiation RNA polymerase II (Pol II) has to locate the transcription start site (TSS) of a specific gene. The accessibility of the DNA plays an important role in this process. While dense chromatin is a barrier for the transcription machinery, a more open chromatin state facilitates binding of Pol II to the DNA. These chromatin changes are induced by alterations of the nucleosome stability through histone variant incorporation or post-translational modifications (PTMs) of the histone tails (e.g. acetylation, methylation).

In Trypanosoma brucei, the causative agent of human African trypanosomiasis, protein-coding genes are arranged in long polycistronic transcription units (PTUs) and no Pol II promoter motifs have been identified at the TSSs. However at TSSs less stable nucleosomes containing the histone variants H2A.Z and H2B.V are enriched.  This finding suggests that the formation of an open chromatin structure facilitates the binding of the transcription machinery to the TSSs and enables thereby transcription initiation. The mechanisms responsible for the targeted deposition of histone variants to specific genomic loci are not well understood in any organism. However, it has been suggested that histone acetylation is involved in directing chromatin-modifying complexes to TSSs.

During my PhD I want to identify the enzymes responsible for the targeted histone deposition to the TSSs and the role of histone acetylation within this process in T. brucei. Given the important, evolutionarily conserved role of nucleosome composition in gene regulation, my findings will help to answer one of the basic mechanisms involved in eukaryotic transcription initiation.