Yildirim, EdaSadreyev, RuslanPinter, Stefan F.Lee, Jeannie2014-03-012013Yildirim, Eda, Ruslan I. Sadreyev, Stefan F. Pinter, and Jeannie T. Lee. 2013. “X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription.” Nature structural & molecular biology 19 (1): 56-61. doi:10.1038/nsmb.2195. http://dx.doi.org/10.1038/nsmb.2195.1545-9993http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855794Dosage compensation in mammals occurs at two levels. In addition to balancing X-chromosome dosage between males and females via X-inactivation, mammals also balance dosage of Xs and autosomes. It has been proposed that X-autosome equalization occurs by upregulation of Xa (active X). To investigate mechanism, we perform allele-specific ChIP-seq for chromatin epitopes and analyze RNA-seq data. The hypertranscribed Xa demonstrates enrichment of active chromatin marks relative to autosomes. We derive predictive models for relationships among POL-II, active mark densities, and gene expression, and suggest that Xa upregulation involves increased transcription initiation and elongation. Enrichment of active marks on Xa does not scale proportionally with transcription output, a disparity explained by nonlinear quantitative dependencies among active histone marks, POL-II occupancy, and transcription. Significantly, the trend of nonlinear upregulation also occurs on autosomes. Thus, Xa upregulation involves combined increases of active histone marks and POL-II occupancy, without invoking X-specific dependencies between chromatin states and transcription.en-USJournal Article2014-03-0110.1038/nsmb.2195