Transposable elements have rewired the core regulatory network of human embryonic stem cells.
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.
Computational and Mathematical Biology, Genome Institute of Singapore, Singapore, Singapore.
Galih
G
Kunarso
Na-Yu
NY
Chia
Justin
J
Jeyakani
Catalina
C
Hwang
Xinyi
X
Lu
Yun-Shen
YS
Chan
Huck-Hui
HH
Ng
Guillaume
G
Bourque
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D000076246:CCCTC-Binding Factor; D004251:DNA Transposable Elements / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; D004251:DNA Transposable Elements; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins