Back to Search
Start Over
CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation
- Source :
- Nucleic Acids Research
- Publication Year :
- 2014
- Publisher :
- Oxford University Press (OUP), 2014.
-
Abstract
- CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF's binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site.
- Subjects :
- CCCTC-Binding Factor
Computational biology
Gene Regulation, Chromatin and Epigenetics
Biology
Genome
chemistry.chemical_compound
Mice
03 medical and health sciences
0302 clinical medicine
Gene expression
Genetics
Animals
Regulatory Elements, Transcriptional
Binding site
Nucleotide Motifs
Cells, Cultured
Embryonic Stem Cells
030304 developmental biology
Sequence (medicine)
0303 health sciences
Binding Sites
Cell Differentiation
Embryonic stem cell
In vitro
Ctcf binding
Repressor Proteins
chemistry
Gene Expression Regulation
CTCF
030220 oncology & carcinogenesis
Nucleic acid
Corrigendum
DNA
Protein Binding
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....41b9af642a7701811380f271aef69d70