A novel role of Rad26 in dynamic chromatin disassembly during transcriptional elonagtion in vivo

Abstract

Cockayne Syndrome group B (CSB) is a DNA dependent ATPase in human, and plays an important role in transcription as well as transcription‐coupled repair (TCR). Mutations in CSB gene lead to cockayne syndrome (CS) charaterised by many traits reminiscient of normal aging. Deciphering the molecular roles of CSB is, thus, essential for disease management and understanding the causes of general aging and related ailments. However, the precise in vivo modes of action of CSB in regulation of transcription and TCR are not yet clearly understood. In this study, we show that the yeast homologue (Rad26) of CSB specifically associates with the coding regions of transcriptionally active genes, and promotes association of elongating RNA polymerase II (RNAPII). However, Rad26 does not control the recruitment of initiating RNAPII or formation of the pre‐initiation complex at the promoter. Intriguingly, we also find that Rad26 enhances the eviction of histone H2A‐H2B dimer, but not histone H3‐H4 tetramer, from the coding regions of active genes. These results, together, demonstrate for the first time the distinct function of Rad26 in promoting specific eviction of histone H2A‐H2B dimer during transcriptional elongation. This work was supported by Mallinckrodt Foundation.