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- EMDB-10392: Structure of human Sox2 transcription factor in complex with a nu... -
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Basic information
Entry | Database: EMDB / ID: EMD-10392 | ||||||||||||
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Title | Structure of human Sox2 transcription factor in complex with a nucleosome | ||||||||||||
![]() | Structure of human Sox2 transcription factor in complex with a nucleosome | ||||||||||||
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![]() | Nucleosome / DNA / histones / Sox2 / transcription factor / pioneer factor / NUCLEAR PROTEIN | ||||||||||||
Function / homology | ![]() glial cell fate commitment / regulation of myofibroblast cell apoptotic process / Formation of the posterior neural plate / regulation of cysteine-type endopeptidase activity involved in apoptotic process / POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation / Formation of the anterior neural plate / adenohypophysis development / response to oxygen-glucose deprivation / endodermal cell fate specification / negative regulation of cell cycle G1/S phase transition ...glial cell fate commitment / regulation of myofibroblast cell apoptotic process / Formation of the posterior neural plate / regulation of cysteine-type endopeptidase activity involved in apoptotic process / POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation / Formation of the anterior neural plate / adenohypophysis development / response to oxygen-glucose deprivation / endodermal cell fate specification / negative regulation of cell cycle G1/S phase transition / POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation / Specification of the neural plate border / pituitary gland development / positive regulation of cell-cell adhesion / Transcriptional Regulation by MECP2 / Transcriptional regulation of pluripotent stem cells / eye development / neuronal stem cell population maintenance / tissue regeneration / Germ layer formation at gastrulation / response to growth factor / miRNA binding / somatic stem cell population maintenance / inner ear development / negative regulation of neuron differentiation / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / heterochromatin organization / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / forebrain development / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere organization / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / PRC2 methylates histones and DNA / innate immune response in mucosa / Defective pyroptosis / Deactivation of the beta-catenin transactivating complex / HDACs deacetylate histones / positive regulation of cell differentiation / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / negative regulation of canonical Wnt signaling pathway / neuron differentiation / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / HDMs demethylate histones / brain development / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / PKMTs methylate histone lysines / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / response to wounding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / osteoblast differentiation / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / UCH proteinases / negative regulation of epithelial cell proliferation / nucleosome / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / Processing of DNA double-strand break ends / antibacterial humoral response / Senescence-Associated Secretory Phenotype (SASP) / regulation of gene expression / DNA-binding transcription activator activity, RNA polymerase II-specific / Interleukin-4 and Interleukin-13 signaling Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.1 Å | ||||||||||||
![]() | Dodonova SO / Zhu F | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function. Authors: Svetlana O Dodonova / Fangjie Zhu / Christian Dienemann / Jussi Taipale / Patrick Cramer / ![]() ![]() Abstract: 'Pioneer' transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming. Pioneer factors can bind nucleosomal DNA to enable gene expression from regions ...'Pioneer' transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming. Pioneer factors can bind nucleosomal DNA to enable gene expression from regions of the genome with closed chromatin. SOX2 is a prominent pioneer factor that is essential for pluripotency and self-renewal of embryonic stem cells. Here we report cryo-electron microscopy structures of the DNA-binding domains of SOX2 and its close homologue SOX11 bound to nucleosomes. The structures show that SOX factors can bind and locally distort DNA at superhelical location 2. The factors also facilitate detachment of terminal nucleosomal DNA from the histone octamer, which increases DNA accessibility. SOX-factor binding to the nucleosome can also lead to a repositioning of the N-terminal tail of histone H4 that includes residue lysine 16. We speculate that this repositioning is incompatible with higher-order nucleosome stacking, which involves contacts of the H4 tail with a neighbouring nucleosome. Our results indicate that pioneer transcription factors can use binding energy to initiate chromatin opening, and thereby facilitate nucleosome remodelling and subsequent transcription. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 9.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 26.8 KB 26.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7 KB | Display | ![]() |
Images | ![]() | 136.5 KB | ||
Filedesc metadata | ![]() | 7.7 KB | ||
Others | ![]() ![]() | 9.7 MB 9.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 758.8 KB | Display | ![]() |
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Full document | ![]() | 758.4 KB | Display | |
Data in XML | ![]() | 12.4 KB | Display | |
Data in CIF | ![]() | 15.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6t7bMC ![]() 6t78C ![]() 6t79C ![]() 6t7aC ![]() 6t7cC ![]() 6t7dC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of human Sox2 transcription factor in complex with a nucleosome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: half map 1
File | emd_10392_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_10392_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Structure of human Sox2 transcription factor in complex with a nu...
+Supramolecule #1: Structure of human Sox2 transcription factor in complex with a nu...
+Supramolecule #2: Histone H2A type 1, H2B type 1-K, H3.2, H4 and SOX2
+Supramolecule #3: DNA
+Macromolecule #1: Histone H3.2
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1-B/E
+Macromolecule #4: Histone H2B type 1-K
+Macromolecule #7: Transcription factor SOX-2
+Macromolecule #5: DNA (147-MER)
+Macromolecule #6: DNA (147-MER)
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.15 mg/mL | |||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R2/1 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 120 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.039 kPa / Details: 0.39 mB pressure, 25 mA | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 289 K / Instrument: FEI VITROBOT MARK IV Details: The sample was applied onto glow-discharged Quantifoil holey carbon grids. The grids were blotted from both sides for 5-10 seconds at 16*C in a chamber at 100% humidity and plunge-frozen ...Details: The sample was applied onto glow-discharged Quantifoil holey carbon grids. The grids were blotted from both sides for 5-10 seconds at 16*C in a chamber at 100% humidity and plunge-frozen into liquid ethane using a manual plunger.. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 30 eV |
Details | At least 50% of the data were collected at 25* stage tilt in order to partially compensate for preferred orientation of particles on the grid, and to improve angular distribution. |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Average electron dose: 1.125 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |