Co-dependency of H2B monoubiquitination and nucleosome re-assembly on Chd1

Monoubiquitination of histone H2B on lysine 123  (H2BK123ub) is a transient histone modification considered to be essential for establishing H3K4 and H3K79 trimethylation by Set1/COMPASS and Dot1, respectively.  Many of the factors such as Rad6/Bre1, the Paf1 complex, and the Bur1/Bur2 complex were identified to be required for proper histone H3K4 and H3K79 trimethylation, and were shown to function by regulating H2BK123ub levels.  Here, we have identified Chd1 as a factor that is required for proper maintenance of H2B monoubiquitination levels, but not for H3K4 and H3K79 trimethylation.  Loss of Chd1 results in a substantial loss of H2BK123ub levels with little to no effect on the genome-wide pattern of H3K4 and H3K79 trimethylation.   Our data shows that nucleosomal occupancy is reduced in gene bodies in both CHD1 null and K123A backgrounds. We have also demonstrated that Chd1’s function in maintaining H2BK123ub levels is conserved from yeast to human. Our study provides evidence that only small levels of H2BK123ub are necessary for full levels of H3K4 and H3K79 trimethylation in vivo, and points to a role for Chd1 in positively regulating gene expression through promoting nucleosome re-assembly coupled with H2B monoubiquitination. Examination of two histone modifications in wild-type and Chd1 null yeast strains using ChIP-seq. Expression profiling in wild-type and Chd1 null yeast strains using RNA-seq.