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Article: Co-motif discovery identifies an esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells

TitleCo-motif discovery identifies an esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells
Authors
KeywordsBioinformatics
Transcription factors
Esrrb-Sox2
Epiblast stem cells
Embryonic stem cells
Issue Date2013
Citation
Stem Cells, 2013, v. 31, n. 2, p. 269-281 How to Cite?
AbstractTranscription factors (TF) often bind in heterodimeric complexes with each TF recognizing a specific neighboring cis element in the regulatory region of the genome. Comprehension of this DNA motif grammar is opaque, yet recent developments have allowed the interrogation of genome- wide TF binding sites. We reasoned that within this data novel motif grammars could be identified that controlled distinct biological programs. For this purpose, we developed a novel motif-discovery tool termed fexcom that systematically interrogates ChIP-seq data to discover spatially constrained TF-TF composite motifs occurring over short DNA distances. We applied this to the extensive ChIP-seq data available from mouse embryonic stem cells (ESCs). In addition to the well-known and most prevalent sox-oct motif, we also discovered a novel constrained spacer motif for Esrrb and Sox2 with a gap of between 2 and 8 bps that Essrb and Sox2 cobind in a selective fashion. Through the use of knockdown experiments, we argue that the Esrrb-Sox2 complex is an arbiter of gene expression differences between ESCs and epiblast stem cells (EpiSC). A number of genes downregulated upon dual Esrrb/Sox2 knockdown (e.g., Klf4, Klf5, Jam2, Pecam1) are similarly downregulated in the ESC to EpiSC transition and contain the esrrb-sox motif. The prototypical Esrrb-Sox2 target gene, containing an esrrbsox element conserved throughout eutherian and metatherian mammals, is Nr0b1. Through positive regulation of this transcriptional repressor, we argue the Esrrb- Sox2 complex promotes the ESC state through inhibition of the EpiSC transcriptional program and the same trio may also function to maintain trophoblast stem cells. © 2012 AlphaMed Press.
Persistent Identifierhttp://hdl.handle.net/10722/253154
ISSN
2020 Impact Factor: 6.277
2020 SCImago Journal Rankings: 2.159
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHutchins, Andrew Paul-
dc.contributor.authorChoo, Siew Hua-
dc.contributor.authorMistri, Tapan Kumar-
dc.contributor.authorRahmani, Mehran-
dc.contributor.authorWoon, Chow Thai-
dc.contributor.authorNg, Calista Keow Leng-
dc.contributor.authorJauch, Ralf-
dc.contributor.authorRobson, Paul-
dc.date.accessioned2018-05-11T05:38:45Z-
dc.date.available2018-05-11T05:38:45Z-
dc.date.issued2013-
dc.identifier.citationStem Cells, 2013, v. 31, n. 2, p. 269-281-
dc.identifier.issn1066-5099-
dc.identifier.urihttp://hdl.handle.net/10722/253154-
dc.description.abstractTranscription factors (TF) often bind in heterodimeric complexes with each TF recognizing a specific neighboring cis element in the regulatory region of the genome. Comprehension of this DNA motif grammar is opaque, yet recent developments have allowed the interrogation of genome- wide TF binding sites. We reasoned that within this data novel motif grammars could be identified that controlled distinct biological programs. For this purpose, we developed a novel motif-discovery tool termed fexcom that systematically interrogates ChIP-seq data to discover spatially constrained TF-TF composite motifs occurring over short DNA distances. We applied this to the extensive ChIP-seq data available from mouse embryonic stem cells (ESCs). In addition to the well-known and most prevalent sox-oct motif, we also discovered a novel constrained spacer motif for Esrrb and Sox2 with a gap of between 2 and 8 bps that Essrb and Sox2 cobind in a selective fashion. Through the use of knockdown experiments, we argue that the Esrrb-Sox2 complex is an arbiter of gene expression differences between ESCs and epiblast stem cells (EpiSC). A number of genes downregulated upon dual Esrrb/Sox2 knockdown (e.g., Klf4, Klf5, Jam2, Pecam1) are similarly downregulated in the ESC to EpiSC transition and contain the esrrb-sox motif. The prototypical Esrrb-Sox2 target gene, containing an esrrbsox element conserved throughout eutherian and metatherian mammals, is Nr0b1. Through positive regulation of this transcriptional repressor, we argue the Esrrb- Sox2 complex promotes the ESC state through inhibition of the EpiSC transcriptional program and the same trio may also function to maintain trophoblast stem cells. © 2012 AlphaMed Press.-
dc.languageeng-
dc.relation.ispartofStem Cells-
dc.subjectBioinformatics-
dc.subjectTranscription factors-
dc.subjectEsrrb-Sox2-
dc.subjectEpiblast stem cells-
dc.subjectEmbryonic stem cells-
dc.titleCo-motif discovery identifies an esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/stem.1279-
dc.identifier.pmid23169531-
dc.identifier.scopuseid_2-s2.0-84874292408-
dc.identifier.volume31-
dc.identifier.issue2-
dc.identifier.spage269-
dc.identifier.epage281-
dc.identifier.isiWOS:000314873000007-
dc.identifier.issnl1066-5099-

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