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protein dna_rna Protein-protein interface(s) links
Transcription factor PDB id
1gt0
Jmol
Contents
Protein chains
138 a.a. *
80 a.a. *
DNA/RNA
Waters ×90
* Residue conservation analysis
PDB id:
1gt0
Name: Transcription factor
Title: Crystal structure of a pou/hmg/DNA ternary complex
Structure: 5'-d( Tp Tp Cp Tp Tp Tp Gp Tp Tp Tp Gp Gp Ap Tp Gp Cp Tp Ap Ap Tp Gp Gp Gp A)-3'. Chain: a. Other_details: fgf-4 enhancer. 5'-d( Ap Tp Cp Cp Cp Ap Tp Tp Ap Gp Cp Ap Tp Cp Cp Ap Ap Ap Cp Ap Ap Ap Gp A)-3'. Chain: b. Other_details: fgf-4 enhancer. Octamer-binding transcription factor 1.
Source: Synthetic: yes. Mus musculus. Mouse. Organism_taxid: 10090. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.60Å     R-factor:   0.232     R-free:   0.285
Authors: A.Remenyi,M.Wilmanns
Key ref: A.Reményi et al. (2003). Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev, 17, 2048-2059. PubMed id: 12923055 DOI: 10.1101/gad.269303
Date:
09-Jan-02     Release date:   30-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P14859  (PO2F1_HUMAN) -  POU domain, class 2, transcription factor 1
Seq:
Struc: 		 
Seq:
Struc: 		743 a.a.
138 a.a.*
Protein chain
Pfam   ArchSchema ?
P48432  (SOX2_MOUSE) -  Transcription factor SOX-2
Seq:
Struc: 		319 a.a.
80 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     protein binding     4 terms  

 

 
DOI no: 10.1101/gad.269303 Genes Dev 17:2048-2059 (2003)
PubMed id: 12923055  
 
 
Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers.
A.Reményi, K.Lins, L.J.Nissen, R.Reinbold, H.R.Schöler, M.Wilmanns.
 
  ABSTRACT  
 
Members of the POU and SOX transcription factor families exemplify the partnerships established between various transcriptional regulators during early embryonic development. Although functional cooperativity between key regulator proteins is pivotal for milestone decisions in mammalian development, little is known about the underlying molecular mechanisms. In this study, we focus on two transcription factors, Oct4 and Sox2, as their combination on DNA is considered to direct the establishment of the first three lineages in the mammalian embryo. Using experimental high-resolution structure determination, followed by model building and experimental validation, we found that Oct4 and Sox2 were able to dimerize onto DNA in distinct conformational arrangements. We demonstrate that the DNA enhancer region of their target genes is responsible for the correct spatial alignment of glue-like interaction domains on their surface. Interestingly, these surfaces frequently have redundant functions and are instrumental in recruiting various interacting protein partners.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20861000 M.Firczuk, M.Wojciechowski, H.Czapinska, and M.Bochtler (2011).
DNA intercalation without flipping in the specific ThaI-DNA complex.
  Nucleic Acids Res, 39, 744-754.
PDB code: 3ndh
21258368 N.Plachta, T.Bollenbach, S.Pease, S.E.Fraser, and P.Pantazis (2011).
Oct4 kinetics predict cell lineage patterning in the early mammalian embryo.
  Nat Cell Biol, 13, 117-123.  
21048080 B.Fernandez-Tresguerres, S.Cañon, T.Rayon, B.Pernaute, M.Crespo, C.Torroja, and M.Manzanares (2010).
Evolution of the mammalian embryonic pluripotency gene regulatory network.
  Proc Natl Acad Sci U S A, 107, 19955-19960.  
20362541 D.L.van den Berg, T.Snoek, N.P.Mullin, A.Yates, K.Bezstarosti, J.Demmers, I.Chambers, and R.A.Poot (2010).
An Oct4-centered protein interaction network in embryonic stem cells.
  Cell Stem Cell, 6, 369-381.  
20212526 D.Onichtchouk, F.Geier, B.Polok, D.M.Messerschmidt, R.Mössner, B.Wendik, S.Song, V.Taylor, J.Timmer, and W.Driever (2010).
Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.
  Mol Syst Biol, 6, 354.  
20624054 J.A.Lessard, and G.R.Crabtree (2010).
Chromatin regulatory mechanisms in pluripotency.
  Annu Rev Cell Dev Biol, 26, 503-532.  
21103394 J.L.Cox, S.K.Mallanna, X.Luo, and A.Rizzino (2010).
Sox2 uses multiple domains to associate with proteins present in Sox2-protein complexes.
  PLoS One, 5, e15486.  
20870645 M.J.Mason, K.Plath, and Q.Zhou (2010).
Identification of context-dependent motifs by contrasting ChIP binding data.
  Bioinformatics, 26, 2826-2832.  
20334529 R.Rohs, X.Jin, S.M.West, R.Joshi, B.Honig, and R.S.Mann (2010).
Origins of specificity in protein-DNA recognition.
  Annu Rev Biochem, 79, 233-269.  
19922439 S.Reiprich, J.Kriesch, S.Schreiner, and M.Wegner (2010).
Activation of Krox20 gene expression by Sox10 in myelinating Schwann cells.
  J Neurochem, 112, 744-754.  
21170349 T.Martin, S.W.Lu, H.van Tilbeurgh, D.R.Ripoll, C.Dixelius, B.G.Turgeon, and R.Debuchy (2010).
Tracing the origin of the fungal α1 domain places its ancestor in the HMG-box superfamily: implication for fungal mating-type evolution.
  PLoS One, 5, e15199.  
20132009 Y.Q.Li (2010).
Master stem cell transcription factors and signaling regulation.
  Cell Reprogram, 12, 3.  
  20016762 A.Rizzino (2009).
Sox2 and Oct-3/4: A Versatile Pair of Master Regulators that Orchestrate the Self-renewal and Pluripotency of Embryonic Stem Cells by Functioning as Molecular Rheostats.
  Wiley Interdiscip Rev Syst Biol Med, 1, 228-236.  
19542351 I.Chambers, and S.R.Tomlinson (2009).
The transcriptional foundation of pluripotency.
  Development, 136, 2311-2322.  
19221599 J.P.Saxe, A.Tomilin, H.R.Schöler, K.Plath, and J.Huang (2009).
Post-translational regulation of Oct4 transcriptional activity.
  PLoS ONE, 4, e4467.  
19662495 M.Bosnali, B.Münst, M.Thier, and F.Edenhofer (2009).
Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming.
  Cell Mol Life Sci, 66, 3403-3420.  
  19821493 M.P.Ponnusamy, S.Deb, P.Dey, S.Chakraborty, S.Rachagani, S.Senapati, and S.K.Batra (2009).
RNA polymerase II associated factor 1/PD2 maintains self-renewal by its interaction with Oct3/4 in mouse embryonic stem cells.
  Stem Cells, 27, 3001-3011.  
  19706369 N.N.Hoke, F.N.Salloum, K.E.Loesser-Casey, and R.C.Kukreja (2009).
Cardiac regenerative potential of adipose tissue-derived stem cells.
  Acta Physiol Hung, 96, 251-265.  
19020954 Y.Zhu, T.Liu, K.Song, B.Jiang, X.Ma, and Z.Cui (2009).
Collagen-chitosan polymer as a scaffold for the proliferation of human adipose tissue-derived stem cells.
  J Mater Sci Mater Med, 20, 799-808.  
19404993 Y.Zhu, T.Liu, K.Song, X.Fan, X.Ma, and Z.Cui (2009).
Ex vivo expansion of adipose tissue-derived stem cells in spinner flasks.
  Biotechnol J, 4, 1198-1209.  
18522731 A.A.Sharov, S.Masui, L.V.Sharova, Y.Piao, K.Aiba, R.Matoba, L.Xin, H.Niwa, and M.S.Ko (2008).
Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data.
  BMC Genomics, 9, 269.  
18983536 A.L.Cook, and R.A.Sturm (2008).
POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis.
  Pigment Cell Melanoma Res, 21, 611-626.  
18393632 B.Greber, H.Lehrach, and J.Adjaye (2008).
Control of early fate decisions in human ES cells by distinct states of TGFbeta pathway activity.
  Stem Cells Dev, 17, 1065-1077.  
  19052383 C.K.Ng, P.Palasingam, R.Venkatachalam, N.Baburajendran, J.Cheng, R.Jauch, and P.R.Kolatkar (2008).
Purification, crystallization and preliminary X-ray diffraction analysis of the HMG domain of Sox17 in complex with DNA.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1184-1187.  
18710938 D.A.Card, P.B.Hebbar, L.Li, K.W.Trotter, Y.Komatsu, Y.Mishina, and T.K.Archer (2008).
Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells.
  Mol Cell Biol, 28, 6426-6438.  
18212089 D.Tantin, M.Gemberling, C.Callister, and W.Fairbrother (2008).
High-throughput biochemical analysis of in vivo location data reveals novel distinct classes of POU5F1(Oct4)/DNA complexes.
  Genome Res, 18, 631-639.  
18366076 H.Chakravarthy, B.Boer, M.Desler, S.K.Mallanna, T.W.McKeithan, and A.Rizzino (2008).
Identification of DPPA4 and other genes as putative Sox2:Oct-3/4 target genes using a combination of in silico analysis and transcription-based assays.
  J Cell Physiol, 216, 651-662.  
18385377 H.Danno, T.Michiue, K.Hitachi, A.Yukita, S.Ishiura, and M.Asashima (2008).
Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.
  Proc Natl Acad Sci U S A, 105, 5408-5413.  
18348160 J.de Jong, H.Stoop, A.J.Gillis, R.J.van Gurp, G.J.van de Geijn, M.Boer, R.Hersmus, P.T.Saunders, R.A.Anderson, J.W.Oosterhuis, and L.H.Looijenga (2008).
Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications.
  J Pathol, 215, 21-30.  
18772384 M.Doucleff, and G.M.Clore (2008).
Global jumping and domain-specific intersegment transfer between DNA cognate sites of the multidomain transcription factor Oct-1.
  Proc Natl Acad Sci U S A, 105, 13871-13876.  
18348274 M.Morín, A.Viñuela, T.Rivera, M.Villamar, M.A.Moreno-Pelayo, F.Moreno, and I.del Castillo (2008).
A de novo missense mutation in the gene encoding the SOX10 transcription factor in a Spanish sporadic case of Waardenburg syndrome type IV.
  Am J Med Genet A, 146, 1032-1037.  
18539116 S.Lee, B.Lee, K.Joshi, S.L.Pfaff, J.W.Lee, and S.K.Lee (2008).
A regulatory network to segregate the identity of neuronal subtypes.
  Dev Cell, 14, 877-889.  
17324942 B.Boer, J.Kopp, S.Mallanna, M.Desler, H.Chakravarthy, P.J.Wilder, C.Bernadt, and A.Rizzino (2007).
Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes.
  Nucleic Acids Res, 35, 1773-1786.  
17579724 P.A.Campbell, C.Perez-Iratxeta, M.A.Andrade-Navarro, and M.A.Rudnicki (2007).
Oct4 targets regulatory nodes to modulate stem cell function.
  PLoS ONE, 2, e553.  
17625949 V.Lefebvre, B.Dumitriu, A.Penzo-Méndez, Y.Han, and B.Pallavi (2007).
Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors.
  Int J Biochem Cell Biol, 39, 2195-2214.  
16523502 B.Boer, C.T.Bernadt, M.Desler, P.J.Wilder, J.L.Kopp, and A.Rizzino (2006).
Differential activity of the FGF-4 enhancer in F9 and P19 embryonal carcinoma cells.
  J Cell Physiol, 208, 97.  
16919449 B.V.Johnson, J.Rathjen, and P.D.Rathjen (2006).
Transcriptional control of pluripotency: decisions in early development.
  Curr Opin Genet Dev, 16, 447-454.  
16795045 R.Izadpanah, C.Trygg, B.Patel, C.Kriedt, J.Dufour, J.M.Gimble, and B.A.Bunnell (2006).
Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue.
  J Cell Biochem, 99, 1285-1297.  
16582099 S.Wissmüller, T.Kosian, M.Wolf, M.Finzsch, and M.Wegner (2006).
The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors.
  Nucleic Acids Res, 34, 1735-1744.  
15653643 C.Y.Chen, T.P.Ko, T.W.Lin, C.C.Chou, C.J.Chen, and A.H.Wang (2005).
Probing the DNA kink structure induced by the hyperthermophilic chromosomal protein Sac7d.
  Nucleic Acids Res, 33, 430-438.
PDB codes: 1wto 1wtp 1wtq 1wtr 1wtv 1wtw 1wtx 1xyi
15988017 J.L.Chew, Y.H.Loh, W.Zhang, X.Chen, W.L.Tam, L.S.Yeap, P.Li, Y.S.Ang, B.Lim, P.Robson, and H.H.Ng (2005).
Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells.
  Mol Cell Biol, 25, 6031-6046.  
15920534 J.X.Lei, Q.Y.Liu, C.Sodja, J.LeBlanc, M.Ribecco-Lutkiewicz, B.Smith, C.Charlebois, P.R.Walker, and M.Sikorska (2005).
S/MAR-binding properties of Sox2 and its involvement in apoptosis of human NT2 neural precursors.
  Cell Death Differ, 12, 1368-1377.  
15923625 M.Nishimoto, S.Miyagi, T.Yamagishi, T.Sakaguchi, H.Niwa, M.Muramatsu, and A.Okuda (2005).
Oct-3/4 maintains the proliferative embryonic stem cell state via specific binding to a variant octamer sequence in the regulatory region of the UTF1 locus.
  Mol Cell Biol, 25, 5084-5094.  
15760336 M.Wegner (2005).
Secrets to a healthy Sox life: lessons for melanocytes.
  Pigment Cell Res, 18, 74-85.  
16166633 P.Gu, D.LeMenuet, A.C.Chung, M.Mancini, D.A.Wheeler, and A.J.Cooney (2005).
Orphan nuclear receptor GCNF is required for the repression of pluripotency genes during retinoic acid-induced embryonic stem cell differentiation.
  Mol Cell Biol, 25, 8507-8519.  
15332082 A.Reményi, H.R.Schöler, and M.Wilmanns (2004).
Combinatorial control of gene expression.
  Nat Struct Mol Biol, 11, 812-815.  
15349837 C.T.Bernadt, T.Nowling, and A.Rizzino (2004).
Transcription factor Sox-2 inhibits co-activator stimulated transcription.
  Mol Reprod Dev, 69, 260-267.  
15671667 I.Chambers (2004).
The molecular basis of pluripotency in mouse embryonic stem cells.
  Cloning Stem Cells, 6, 386-391.  
14711414 K.Lunde, H.G.Belting, and W.Driever (2004).
Zebrafish pou5f1/pou2, homolog of mammalian Oct4, functions in the endoderm specification cascade.
  Curr Biol, 14, 48-55.  
15542856 S.Futaki, Y.Hayashi, T.Emoto, C.N.Weber, and K.Sekiguchi (2004).
Sox7 plays crucial roles in parietal endoderm differentiation in F9 embryonal carcinoma cells through regulating Gata-4 and Gata-6 expression.
  Mol Cell Biol, 24, 10492-10503.  
15456859 S.Tanaka, Y.Kamachi, A.Tanouchi, H.Hamada, N.Jing, and H.Kondoh (2004).
Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells.
  Mol Cell Biol, 24, 8834-8846.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.