Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers.
Despite the conventional distinction between them, promoters and enhancers share many features in mammals, including divergent transcription and similar modes of transcription factor binding. Here we examine the architecture of transcription initiation through comprehensive mapping of transcription start sites (TSSs) in human lymphoblastoid B cell (GM12878) and chronic myelogenous leukemic (K562) ENCODE Tier 1 cell lines. Using a nuclear run-on protocol called GRO-cap, which captures TSSs for both stable and unstable transcripts, we conduct detailed comparisons of thousands of promoters and enhancers in human cells. These analyses identify a common architecture of initiation, including tightly spaced (110 bp apart) divergent initiation, similar frequencies of core promoter sequence elements, highly positioned flanking nucleosomes and two modes of transcription factor binding. Post-initiation transcript stability provides a more fundamental distinction between promoters and enhancers than patterns of histone modification and association of transcription factors or co-activators. These results support a unified model of transcription initiation at promoters and enhancers.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
Leighton J
LJ
Core
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
André L
AL
Martins
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
Charles G
CG
Danko
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
Colin T
0000000230960833
CT
Waters
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
Adam
A
Siepel
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
John T
JT
Lis
D001402:B-Lymphocytes / Q000166:cytology; D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000737:chemistry; D006801:Humans; D020014:K562 Cells; D008390:Markov Chains; D008957:Models, Genetic; D009707:Nucleosomes / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics*; D012326:RNA Splicing; D012045:Regulatory Sequences, Nucleic Acid; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D012313:RNA