Three Distinct Patterns of Histone H3Y41 Phosphorylation Mark Active Genes

SummaryThe JAK2 tyrosine kinase is a critical mediator of cytokine-induced signaling. It plays a role in the nucleus, where it regulates transcription by phosphorylating histone H3 at tyrosine 41 (H3Y41ph). We used chromatin immunoprecipitation coupled to massively parallel DNA sequencing (ChIP-seq) to define the genome-wide pattern of H3Y41ph in human erythroid leukemia cells. Our results indicate that H3Y41ph is located at three distinct sites: (1) at a subset of active promoters, where it overlaps with H3K4me3, (2) at distal cis-regulatory elements, where it coincides with the binding of STAT5, and (3) throughout the transcribed regions of active, tissue-specific hematopoietic genes. Together, these data extend our understanding of this conserved and essential signaling pathway and provide insight into the mechanisms by which extracellular stimuli may lead to the coordinated regulation of transcription.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Histone H3Y41 phosphorylation is associated with actively transcribed genes ► H3Y41ph correlates with H3K4me3 at the TSS of a subset of active genes ► H3Y41ph and STAT5 binding are coincident at some JAK2/STAT5 target genes ► H3Y41ph blankets the entire transcribed region of active tissue-specific genes