ArticleGenome biology2008
Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells.
Article in Genome biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility.Epigenetics & chromatin · 2015Article
- The most deeply conserved noncoding sequences in plants serve similar functions to those in vertebrates despite large differences in evolutionary rates.The Plant cell · 2014Article
- What does our genome encode?Genome research · 2012Article
- Genomic approaches towards finding cis-regulatory modules in animals.Nature reviews. Genetics · 2012Review
- Chromosome conformation capture uncovers potential genome-wide interactions between human conserved non-coding sequences.PloS one · 2011Article
- A liver enhancer in the fibrinogen gene cluster.Blood · 2011Article
- Article
- Lineage-specific DNA methylation in T cells correlates with histone methylation and enhancer activity.Genome research · 2009Article
- Balanced translocations in mental retardation.Human genetics · 2009Review
- Disease-causing 7.4 kb cis-regulatory deletion disrupting conserved non-coding sequences and their interaction with the FOXL2 promotor: implications for mutation screening.PLoS genetics · 2009Article
- Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.Breast cancer research : BCR · 2009Article
- Identifying transcriptional cis-regulatory modules in animal genomes.Wiley interdisciplinary reviews. Developmental biologyReview
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 4 countries.
Funding
Abstract
backgroundConserved 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.
resultsWe 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.
conclusionsThe 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.