Molecular Biology

Start and Stop Signals

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Science  29 May 2009:
Vol. 324, Issue 5931, pp. 1119
DOI: 10.1126/science.324_1119a

Human sleeping sickness is caused by the parasitic protozoan Trypanosoma brucei, which is transmitted when the tsetse fly bites. As in prokaryotes, the genes in this microorganism are arrayed in large polycistronic transcription units. Despite this unusual organization relative to what is seen in most other eukaryotes, the promoter elements where RNA polymerase II and its associated transcription factors bind have largely eluded identification.

Using the ChIP-seq method, which involves DNA sequencing of chromatin immunoprecipitations, Siegel et al. suggest that Pol II transcription factors look for histone modifications and histone variants. Levels of acetylated histone H4 (H4K10ac) are higher at Pol II transcription start sites. In addition, histone variants H2BV and H2AZ, as well as the bromodomain protein BDF3, colocalize with H4K10ac. The authors also show that decoration with these histone variants correlates with less stable nucleosomes, which would allow for their displacement by transcription initiation complexes. A third feature defined by histone variants, in this instance H3V and H4V, is the transcription termination regions. Finally, G-rich stretches in the sense strand upstream of H4K10ac sites may serve as directional sign-posts for transcription. Hence, Trypanosoma appears to use nucleotide sequence and chromatin structure to mark starts and stops.

Genes Dev. 23, 1063 (2009).

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