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
-
Homeodomain Proteins / metabolism
-
Humans
-
Mice
-
Models, Genetic
-
Nanog Homeobox Protein
-
Octamer Transcription Factor-3 / genetics
-
Octamer Transcription Factor-3 / metabolism
-
Protein Binding
-
RNA Interference
-
Regulatory Sequences, Nucleic Acid / genetics*
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism
-
Species Specificity
Substances
-
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