Histone Variant H2A.Bbd Is Associated with Active Transcription and mRNA Processing in Human Cells

SummaryVariation in chromatin composition and organization often reflects differences in genome function. Histone variants, for example, replace canonical histones to contribute to regulation of numerous nuclear processes including transcription, DNA repair, and chromosome segregation. Here we focus on H2A.Bbd, a rapidly evolving variant found in mammals but not in invertebrates. We report that in human cells, nucleosomes bearing H2A.Bbd form unconventional chromatin structures enriched within actively transcribed genes and characterized by shorter DNA protection and nucleosome spacing. Analysis of transcriptional profiles from cells depleted for H2A.Bbd demonstrated widespread changes in gene expression with a net downregulation of transcription and disruption of normal mRNA splicing patterns. In particular, we observed changes in exon inclusion rates and increased presence of intronic sequences in mRNA products upon H2A.Bbd depletion. Taken together, our results indicate that H2A.Bbd is involved in formation of a specific chromatin structure that facilitates both transcription and initial mRNA processing.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (179 K)Download as PowerPoint slideHighlights► H2A.Bbd nucleosomes organize less DNA than canonical nucleosomes in vivo ► H2A.Bbd is enriched within active genes and copurifies with elongating RNA Pol II ► H2A.Bbd associates with spliceosome components, particularly those in the U2 snRNP ► H2A.Bbd depletion alters transcriptional output and leads to aberrant mRNA splicing