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Abstract
We describe the results of a genome-wide analysis of human cells that suggests that
most protein-coding genes, including most genes thought to be transcriptionally inactive,
experience transcription initiation. We found that nucleosomes with H3K4me3 and H3K9,14Ac
modifications, together with RNA polymerase II, occupy the promoters of most protein-coding
genes in human embryonic stem cells. Only a subset of these genes produce detectable
full-length transcripts and are occupied by nucleosomes with H3K36me3 modifications,
a hallmark of elongation. The other genes experience transcription initiation but
show no evidence of elongation, suggesting that they are predominantly regulated at
postinitiation steps. Genes encoding most developmental regulators fall into this
group. Our results also identify a class of genes that are excluded from experiencing
transcription initiation, at which mechanisms that prevent initiation must predominate.
These observations extend to differentiated cells, suggesting that transcription initiation
at most genes is a general phenomenon in human cells.