Spt6: Two fundamentally distinct functions in the regulation of histone modification

As posttranslational modifications of histones H3 and H4 determine the state of chromatin in cis, these histones should remain attached to template DNA during transcription in order to maintain the state of chromatin. RNA polymerase II itself can transcribe the nucleosome template without changing nucleosome positioning. However, it was uncertain whether Spt6, a highly conserved polymerase-associated histone chaperone, prevents “preexisting” histone molecules from being dissociated from template DNA during transcription. We recently showed that Spt6 prevents transcription-coupled loss of posttranslationally modified histone H3. Taking previous studies into account, we would like to propose here that Spt6 has two fundamentally distinct functions in the regulation of histone modification: one is to act as a platform for histone modifiers and the other is to act as a molecular liaison between histone molecules and template DNA to prevent cotranscriptional dissociation of preexisting histones in order to maintain locus-specific modifications.