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- W1619602040 abstract "Despite significant progress in structural and functional characterization of human genome, understanding of mechanisms underlying the genetic basis of human phenotypic uniqueness remains limited. We report that non-randomly distributed transposable element-derived sequences, most notably HERV-H/LTR7 and L1HS, are associated with creation of 99.8% unique to human transcription factor binding sites in genome of embryonic stem cells (ESC). 4,094 unique to human regulatory loci display selective and site-specific binding of critical regulators (NANOG, POU5F1, CTCF, Lamin B1) and are preferentially placed within the matrix of transcriptionally active DNA segments hyper-methylated in ESC. Unique to human NANOG-binding sites are enriched near the rapidly evolving in primates protein-coding genes regulating brain size, pluripotency lncRNAs, hESC enhancers, and 5-hydroxymethylcytosine-harboring regions immediately adjacent to binding sites. We propose a proximity placement model explaining how 33-47% excess of NANOG and POU5F1 proteins immobilized on a DNA scaffold may play a functional role at distal regulatory elements." @default.
- W1619602040 created "2016-06-24" @default.
- W1619602040 creator A5083792252 @default.
- W1619602040 date "2014-04-03" @default.
- W1619602040 modified "2023-09-27" @default.
- W1619602040 title "Identification and characterization of unique to human regulatory sequences in embryonic stem cells reveal associations with transposable elements, distal enhancers, non-coding RNA, and DNA methylation-driven mechanisms of genome editing" @default.
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