期刊
GENOME BIOLOGY
卷 9, 期 12, 页码 -出版社
BMC
DOI: 10.1186/gb-2008-9-12-r168
关键词
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资金
- NCCR Frontiers in Genetics doctoral school
- Swiss National Science Foundation
- NCCR Frontiers in Genetics
- European Commission
- Jerome Lejeune
- Childcare (SEA) Foundations
- National Institute of General Medical Sciences
- National Human Genome Research Institute
- NIH [HG003161, GM071923]
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG003161] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM079123] Funding Source: NIH RePORTER
Background: Conserved non-coding sequences in the human genome are approximately tenfold more abundant than known genes, and have been hypothesized to mark the locations of cis-regulatory elements. However, the global contribution of conserved non-coding sequences to the transcriptional regulation of human genes is currently unknown. Deeply conserved elements shared between humans and teleost fish predominantly flank genes active during morphogenesis and are enriched for positive transcriptional regulatory elements. However, such deeply conserved elements account for <1% of the conserved non-coding sequences in the human genome, which are predominantly mammalian. Results: We explored the regulatory potential of a large sample of these 'common' conserved non-coding sequences using a variety of classic assays, including chromatin remodeling, and enhancer/repressor and promoter activity. When tested across diverse human model cell types, we find that the fraction of experimentally active conserved non-coding sequences within any given cell type is low (approximately 5%), and that this proportion increases only modestly when considered collectively across cell types. Conclusions: The results suggest that classic assays of cis-regulatory potential are unlikely to expose the functional potential of the substantial majority of mammalian conserved non-coding sequences in the human genome.
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