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Hum Mol Genet. 2011 Oct 15;20(20):3964-73. doi: 10.1093/hmg/ddr315. Epub 2011 Jul 26.

Allele-specific distribution of RNA polymerase II on female X chromosomes.

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  • 1Genome Biology Group, Duke Institute for Genome Sciences & Policy, Duke University, CIEMAS 2376, 101 Science Drive, Durham, 27708 NC, USA.

Abstract

While the distribution of RNA polymerase II (PolII) in a variety of complex genomes is correlated with gene expression, the presence of PolII at a gene does not necessarily indicate active expression. Various patterns of PolII binding have been described genome wide; however, whether or not PolII binds at transcriptionally inactive sites remains uncertain. The two X chromosomes in female cells in mammals present an opportunity to examine each of the two alleles of a given locus in both active and inactive states, depending on which X chromosome is silenced by X chromosome inactivation. Here, we investigated PolII occupancy and expression of the associated genes across the active (Xa) and inactive (Xi) X chromosomes in human female cells to elucidate the relationship of gene expression and PolII binding. We find that, while PolII in the pseudoautosomal region occupies both chromosomes at similar levels, it is significantly biased toward the Xa throughout the rest of the chromosome. The general paucity of PolII on the Xi notwithstanding, detectable (albeit significantly reduced) binding can be observed, especially on the evolutionarily younger short arm of the X. PolII levels at genes that escape inactivation correlate with the levels of their expression; however, additional PolII sites can be found at apparently silenced regions, suggesting the possibility of a subset of genes on the Xi that are poised for expression. Consistent with this hypothesis, we show that a high proportion of genes associated with PolII-accessible sites, while silenced in GM12878, are expressed in other female cell lines.

PMID:
21791549
[PubMed - indexed for MEDLINE]
PMCID:
PMC3177651
Free PMC Article

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