Tousled kinase TLK1B counteracts the effect of Asf1 in inhibition of histone H3–H4 tetramer formation

Abstract

BackgroundThe Tousled-like kinases (TLKs) function in processes of chromatin assembly, including replication, transcription, repair, and chromosome segregation. TLK1 interacts specifically with the chromatin assembly factor Asf1, a histone H3–H4 chaperone, and with Rad9, a protein involved in DNA repair. Asf1 binds to the H3–H4 dimer at the same interface that is used for formation of the core tetramer, and hence Asf1 is implicated in disruption of the tetramer during transcription, although Asf1 also has a function in chromatin assembly during replication and repair.FindingsWe have used protein crosslinking with purified components to probe the interaction between H3, H4, Asf1, and TLK1B. We found that TLK1B, by virtue of its binding to Asf1, can restore formation of H3–H4 tetramers that is sterically prevented by adding Asf1.ConclusionWe suggest that TLK1B binds to Asf1 in a manner that interferes with its binding to the H3–H4 dimer, thereby allowing for H3–H4 tetramerization. A description of the function of TLK1 and Asf1 in chromatin remodeling is presented.