X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription.

Published

Journal Article

Dosage 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 occupancy, active mark densities and gene expression, and we 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. Notably, 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.

Full Text

Duke Authors

Cited Authors

  • Yildirim, E; Sadreyev, RI; Pinter, SF; Lee, JT

Published Date

  • December 4, 2011

Published In

Volume / Issue

  • 19 / 1

Start / End Page

  • 56 - 61

PubMed ID

  • 22139016

Pubmed Central ID

  • 22139016

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

International Standard Serial Number (ISSN)

  • 1545-9993

Digital Object Identifier (DOI)

  • 10.1038/nsmb.2195

Language

  • eng