Histone H3 Variant Regulates RNA Polymerase II Transcription Termination and Dual Strand Transcription of siRNA Loci in Trypanosoma brucei

摘要: Base J, β-D-glucosyl-hydroxymethyluracil, is a chromatin modification of thymine in the nuclear DNA flagellated protozoa order Kinetoplastida. In Trypanosoma brucei, J enriched, along with histone H3 variant (H3.V), at sites involved RNA Polymerase (RNAP) II termination and telomeric regulating surface glycoprotein gene (VSG) transcription by RNAP I. Reduction T. brucei indicated role regulation termination, where loss specific within polycistronic clusters led to read-through increased expression downstream genes. We now demonstrate that H3.V leads similar defects Gene derepression intensified upon subsequent knockout. mRNA-seq indicates includes VSG genes silent I transcribed clusters, suggesting an important for repression antigenic variation. Furthermore, regions overlapping end convergent nascent siRNA production. Our results suggest base can act independently as well synergistically regulate coding non-coding RNAs depending on context (and transcribing polymerase). As such these studies provide first direct evidence negatively influencing elongation promote termination.