Transposable Elements and DNA Methylation Create in Embryonic Stem Cells Human-Specific Regulatory Sequences Associated with Distal Enhancers and Noncoding RNAs.
Bottom Line: Despite significant progress in the structural and functional characterization of the human genome, understanding of the mechanisms underlying the genetic basis of human phenotypic uniqueness remains limited.Preliminary estimates suggest that emergence of one novel NANOG-binding site detectable in hESC required 466 years of evolution.A proximity placement model is proposed explaining how a 33-47% excess of NANOG, CTCF, and POU5F1 proteins immobilized on a DNA scaffold may play a functional role at distal regulatory elements.
Affiliation: Institute of Engineering in Medicine, University of California, San Diego The Stanford University School of Medicine, Department of Surgery, Stanford, California email@example.com firstname.lastname@example.org.Show MeSH
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Mentions: This analysis reveals an interindividual variability in degree of conservation of human-specific NANOG-binding sites ranging from 31.4% to 43.6% in individual genomes of Modern Humans. Conservation of full-length human-specific NANOG-binding sequences was 31.4% in Papua (New Guinean), 35.7% in Han (Chinese), 39.2% in Yoruba (West Africa), 43.3% in French (Western Europe), and 43.6% in San (Southern Africa). The sequence homology analysis identifies 152 sequences (18.4%) that are conserved in all five individual human genomes, whereas 58.1% of human-specific NANOG-binding sites are conserved in at least one individual genome of Modern Humans (fig. 6). In striking contrast, only 32 sequences (4.3%) of human ESC-specific NANOG-binding sites are conserved in at least one Neanderthals genome, suggesting that a majority of human ESC-specific NANOG-binding sites (95.7%; 794 sequences) emerged in Modern Humans after the Modern Humans/Neanderthals split approximately 370,000 years ago (Noonan et al. 2006). Emergence in genomes of Modern Humans of 794 regulatory sequences during 370,000 years implies that 2.15 novel NANOG-binding sites evolved in hESC genome every 1,000 years or one novel NANOG-binding site per 466 years of evolution (table 4; fig. 6).Fig. 6.—
Affiliation: Institute of Engineering in Medicine, University of California, San Diego The Stanford University School of Medicine, Department of Surgery, Stanford, California email@example.com firstname.lastname@example.org.