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

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells
นักวิจัย : Hutchins, Andrew Paul , Choo, Siew Hua , Mistri, Tapan Kumar , Rahmani, Mehran , Woon, Chow Thai , Ng, Calista Keow Leng , Jauch, Ralf , Robson, Paul
คำค้น : DRNTU::Science::Biological sciences::Cytology.
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2555
อ้างอิง : Hutchins, A. P., Choo, S. H., Mistri, T. K., Rahmani, M., Woon, C. T., Ng, C. K. L., et al. (2013). Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells. Stem cells, 31(2), 269-281. , 1066-5099 , http://hdl.handle.net/10220/18922 , http://dx.doi.org/10.1002/stem.1279
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Stem cells
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

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.

บรรณานุกรม :
Hutchins, Andrew Paul , Choo, Siew Hua , Mistri, Tapan Kumar , Rahmani, Mehran , Woon, Chow Thai , Ng, Calista Keow Leng , Jauch, Ralf , Robson, Paul . (2555). Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Hutchins, Andrew Paul , Choo, Siew Hua , Mistri, Tapan Kumar , Rahmani, Mehran , Woon, Chow Thai , Ng, Calista Keow Leng , Jauch, Ralf , Robson, Paul . 2555. "Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Hutchins, Andrew Paul , Choo, Siew Hua , Mistri, Tapan Kumar , Rahmani, Mehran , Woon, Chow Thai , Ng, Calista Keow Leng , Jauch, Ralf , Robson, Paul . "Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2555. Print.
Hutchins, Andrew Paul , Choo, Siew Hua , Mistri, Tapan Kumar , Rahmani, Mehran , Woon, Chow Thai , Ng, Calista Keow Leng , Jauch, Ralf , Robson, Paul . Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2555.