Abstract
Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only approximately 5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.
MeSH Terms
Animals
Binding Sites/genetics
CCCTC-Binding Factor
DNA Transposable Elements/genetics
Embryonic Stem Cells/metabolism
Gene Expression Profiling
Gene Regulatory Networks
Genome-Wide Association Study
Homeodomain Proteins/genetics,metabolism
Humans
Mice
Models, Genetic
Nanog Homeobox Protein
Octamer Transcription Factor-3/genetics,metabolism
Protein Binding
RNA Interference
Regulatory Sequences, Nucleic Acid/genetics
Repressor Proteins/genetics,metabolism
Species Specificity
Chemicals
CCCTC-Binding Factor
CTCF protein, human
Ctcf protein, mouse
DNA Transposable Elements
Homeodomain Proteins
NANOG protein, human
Nanog Homeobox Protein
Nanog protein, mouse
Octamer Transcription Factor-3
POU5F1 protein, human
Pou5f1 protein, mouse
Repressor Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kunarso Galih
Computational and Mathematical Biology, Genome Institute of Singapore, Singapore, Singapore.
Chia Na-Yu
Jeyakani Justin
Hwang Catalina
Lu Xinyi
Chan Yun-Shen
Ng Huck-Hui
Bourque Guillaume
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