English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Transcription 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  esrrb‐sox  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. S TEM  C ELLS  2013;31:269–281

stem cells

Co‐Motif Discovery Identifies an Esrrb‐Sox2‐DNA Ternary Complex as a Mediator of Transcriptional Differences Between Mouse Embryonic and Epiblast Stem Cells