+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-29843 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human Oct4 bound to nucleosome with human nMatn1 sequence | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | Oct4 / Nucleosome / Histone / nMatn1 DNA / DNA BINDING PROTEIN-DNA complex | |||||||||
Function / homology | Function and homology information cell fate commitment involved in formation of primary germ layer / cardiac cell fate determination / POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation / Formation of the anterior neural plate / endodermal-mesodermal cell signaling / endodermal cell fate specification / regulation of asymmetric cell division / Specification of primordial germ cells / heart induction / POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation ...cell fate commitment involved in formation of primary germ layer / cardiac cell fate determination / POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation / Formation of the anterior neural plate / endodermal-mesodermal cell signaling / endodermal cell fate specification / regulation of asymmetric cell division / Specification of primordial germ cells / heart induction / POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation / Specification of the neural plate border / Transcriptional regulation of pluripotent stem cells / Germ layer formation at gastrulation / miRNA binding / somatic stem cell population maintenance / blastocyst development / anatomical structure morphogenesis / BMP signaling pathway / negative regulation of miRNA transcription / DNA-binding transcription repressor activity, RNA polymerase II-specific / response to wounding / structural constituent of chromatin / sequence-specific double-stranded DNA binding / nucleosome / positive regulation of canonical Wnt signaling pathway / nucleosome assembly / regulation of gene expression / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / sequence-specific DNA binding / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / protein heterodimerization activity / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / ubiquitin protein ligase binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / mitochondrion / DNA binding / RNA binding / nucleoplasm / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Xenopus laevis (African clawed frog) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.3 Å | |||||||||
Authors | Sinha KK / Bilokapic S / Du Y / Malik D / Halic M | |||||||||
Funding support | United States, 2 items
| |||||||||
Citation | Journal: Nature / Year: 2023 Title: Histone modifications regulate pioneer transcription factor cooperativity. Authors: Kalyan K Sinha / Silvija Bilokapic / Yongming Du / Deepshikha Malik / Mario Halic / Abstract: Pioneer transcription factors have the ability to access DNA in compacted chromatin. Multiple transcription factors can bind together to a regulatory element in a cooperative way, and cooperation ...Pioneer transcription factors have the ability to access DNA in compacted chromatin. Multiple transcription factors can bind together to a regulatory element in a cooperative way, and cooperation between the pioneer transcription factors OCT4 (also known as POU5F1) and SOX2 is important for pluripotency and reprogramming. However, the molecular mechanisms by which pioneer transcription factors function and cooperate on chromatin remain unclear. Here we present cryo-electron microscopy structures of human OCT4 bound to a nucleosome containing human LIN28B or nMATN1 DNA sequences, both of which bear multiple binding sites for OCT4. Our structural and biochemistry data reveal that binding of OCT4 induces changes to the nucleosome structure, repositions the nucleosomal DNA and facilitates cooperative binding of additional OCT4 and of SOX2 to their internal binding sites. The flexible activation domain of OCT4 contacts the N-terminal tail of histone H4, altering its conformation and thus promoting chromatin decompaction. Moreover, the DNA-binding domain of OCT4 engages with the N-terminal tail of histone H3, and post-translational modifications at H3K27 modulate DNA positioning and affect transcription factor cooperativity. Thus, our findings suggest that the epigenetic landscape could regulate OCT4 activity to ensure proper cell programming. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_29843.map.gz | 23.5 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-29843-v30.xml emd-29843.xml | 24.3 KB 24.3 KB | Display Display | EMDB header |
Images | emd_29843.png | 74.4 KB | ||
Filedesc metadata | emd-29843.cif.gz | 6.8 KB | ||
Others | emd_29843_half_map_1.map.gz emd_29843_half_map_2.map.gz | 23.5 MB 23.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-29843 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29843 | HTTPS FTP |
-Validation report
Summary document | emd_29843_validation.pdf.gz | 923.7 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_29843_full_validation.pdf.gz | 923.2 KB | Display | |
Data in XML | emd_29843_validation.xml.gz | 10.6 KB | Display | |
Data in CIF | emd_29843_validation.cif.gz | 12.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29843 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29843 | HTTPS FTP |
-Related structure data
Related structure data | 8g88MC 8g86C 8g87C 8g8bC 8g8eC 8g8gC C: citing same article (ref.) M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_29843.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.61 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #1
File | emd_29843_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_29843_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Nucleosome with Human nMatn1 sequence
Entire | Name: Nucleosome with Human nMatn1 sequence |
---|---|
Components |
|
-Supramolecule #1: Nucleosome with Human nMatn1 sequence
Supramolecule | Name: Nucleosome with Human nMatn1 sequence / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#7 |
---|---|
Source (natural) | Organism: Xenopus laevis (African clawed frog) |
-Macromolecule #1: Histone H3
Macromolecule | Name: Histone H3 / type: protein_or_peptide / ID: 1 / Details: Histone H3.2|Xenopus laevis / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 15.30393 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: ARTKQTARKS TGGKAPRKQL ATKAARKSAP ATGGVKKPHR YRPGTVALRE IRRYQKSTEL LIRKLPFQRL VREIAQDFKT DLRFQSSAV MALQEASEAY LVALFEDTNL CAIHAKRVTI MPKDIQLARR IRGERA UniProtKB: Histone H3.2 |
-Macromolecule #2: Histone H4
Macromolecule | Name: Histone H4 / type: protein_or_peptide / ID: 2 / Details: Histone H4|Xenopus laevis / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 11.263231 KDa |
Recombinant expression | Organism: Escherichia phage HY01 (virus) |
Sequence | String: SGRGKGGKGL GKGGAKRHRK VLRDNIQGIT KPAIRRLARR GGVKRISGLI YEETRGVLKV FLENVIRDAV TYTEHAKRKT VTAMDVVYA LKRQGRTLYG FGG UniProtKB: Histone H4 |
-Macromolecule #3: Histone H2A
Macromolecule | Name: Histone H2A / type: protein_or_peptide / ID: 3 / Details: Histone H2A|Xenopus laevis / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 13.978241 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: SGRGKQGGKT RAKAKTRSSR AGLQFPVGRV HRLLRKGNYA ERVGAGAPVY LAAVLEYLTA EILELAGNAA RDNKKTRIIP RHLQLAVRN DEELNKLLGR VTIAQGGVLP NIQSVLLPKK TESSKSAKSK UniProtKB: Histone H2A |
-Macromolecule #4: Histone H2B
Macromolecule | Name: Histone H2B / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Xenopus laevis (African clawed frog) |
Molecular weight | Theoretical: 13.524752 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: AKSAPAPKKG SKKAVTKTQK KDGKKRRKTR KESYAIYVYK VLKQVHPDTG ISSKAMSIMN SFVNDVFERI AGEASRLAHY NKRSTITSR EIQTAVRLLL PGELAKHAVS EGTKAVTKYT SAK UniProtKB: Histone H2B 1.1 |
-Macromolecule #7: POU domain, class 5, transcription factor 1
Macromolecule | Name: POU domain, class 5, transcription factor 1 / type: protein_or_peptide / ID: 7 / Details: human Oct4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 42.299453 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: GSSHHHHHHS SGLVPRGSHM ASMTGGQQMG RDPNSMAGHL ASDFAFSPPP GGGGDGPGGP EPGWVDPRTW LSFQGPPGGP GIGPGVGPG SEVWGIPPCP PPYEFCGGMA YCGPQVGVGL VPQGGLETSQ PEGEAGVGVE SNSDGASPEP CTVTPGAVKL E KEKLEQNP ...String: GSSHHHHHHS SGLVPRGSHM ASMTGGQQMG RDPNSMAGHL ASDFAFSPPP GGGGDGPGGP EPGWVDPRTW LSFQGPPGGP GIGPGVGPG SEVWGIPPCP PPYEFCGGMA YCGPQVGVGL VPQGGLETSQ PEGEAGVGVE SNSDGASPEP CTVTPGAVKL E KEKLEQNP EESQDIKALQ KELEQFAKLL KQKRITLGYT QADVGLTLGV LFGKVFSQTT ICRFEALQLS FKNMCKLRPL LQ KWVEEAD NNENLQEICK AETLVQARKR KRTSIENRVR GNLENLFLQC PKPTLQQISH IAQQLGLEKD VVRVWFCNRR QKG KRSSSD YAQREDFEAA GSPFSGGPVS FPLAPGPHFG TPGYGSPHFT ALYSSVPFPE GEAFPPVSVT TLGSPMHSN UniProtKB: POU domain, class 5, transcription factor 1 |
-Macromolecule #5: nMATn1 DNA top strand (168-MER)
Macromolecule | Name: nMATn1 DNA top strand (168-MER) / type: dna / ID: 5 / Details: nMATn1 DNA top strand / Number of copies: 1 / Classification: DNA |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 56.93359 KDa |
Sequence | String: (DA)(DC)(DA)(DT)(DG)(DC)(DA)(DC)(DA)(DC) (DA)(DT)(DG)(DC)(DT)(DA)(DA)(DT)(DA)(DT) (DA)(DT)(DG)(DC)(DA)(DC)(DA)(DC)(DA) (DA)(DT)(DG)(DC)(DA)(DC)(DA)(DC)(DA)(DG) (DG) (DT)(DT)(DA)(DA)(DT)(DA) ...String: (DA)(DC)(DA)(DT)(DG)(DC)(DA)(DC)(DA)(DC) (DA)(DT)(DG)(DC)(DT)(DA)(DA)(DT)(DA)(DT) (DA)(DT)(DG)(DC)(DA)(DC)(DA)(DC)(DA) (DA)(DT)(DG)(DC)(DA)(DC)(DA)(DC)(DA)(DG) (DG) (DT)(DT)(DA)(DA)(DT)(DA)(DT)(DA) (DT)(DA)(DC)(DA)(DC)(DA)(DT)(DA)(DC)(DA) (DC)(DA) (DC)(DA)(DC)(DA)(DT)(DG)(DC) (DA)(DC)(DA)(DC)(DA)(DC)(DA)(DC)(DG)(DT) (DG)(DC)(DA) (DC)(DA)(DC)(DA)(DT)(DA) (DT)(DA)(DT)(DG)(DC)(DA)(DC)(DA)(DT)(DG) (DC)(DA)(DT)(DG) (DC)(DA)(DC)(DA)(DC) (DA)(DC)(DG)(DT)(DA)(DT)(DA)(DT)(DG)(DC) (DA)(DC)(DA)(DC)(DA) (DC)(DA)(DT)(DG) (DC)(DA)(DC)(DA)(DT)(DG)(DC)(DA)(DT)(DG) (DC)(DG)(DC)(DA)(DC)(DA) (DT)(DA)(DG) (DT)(DC)(DA)(DC)(DA)(DC)(DA)(DC)(DA)(DT) (DG)(DC)(DA)(DC)(DA)(DC)(DA) (DT)(DT) (DA)(DG)(DC)(DA)(DT)(DA)(DT)(DG)(DC)(DA) (DT)(DA)(DC)(DA)(DC)(DA)(DT)(DA) (DC) (DA)(DT)(DG)(DC)(DA) |
-Macromolecule #6: nMatn1 DNA bottom strand (168-MER)
Macromolecule | Name: nMatn1 DNA bottom strand (168-MER) / type: dna / ID: 6 / Number of copies: 1 / Classification: DNA |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 57.889855 KDa |
Sequence | String: (DT)(DG)(DC)(DA)(DT)(DG)(DT)(DA)(DT)(DG) (DT)(DG)(DT)(DA)(DT)(DG)(DC)(DA)(DT)(DA) (DT)(DG)(DC)(DT)(DA)(DA)(DT)(DG)(DT) (DG)(DT)(DG)(DC)(DA)(DT)(DG)(DT)(DG)(DT) (DG) (DT)(DG)(DA)(DC)(DT)(DA) ...String: (DT)(DG)(DC)(DA)(DT)(DG)(DT)(DA)(DT)(DG) (DT)(DG)(DT)(DA)(DT)(DG)(DC)(DA)(DT)(DA) (DT)(DG)(DC)(DT)(DA)(DA)(DT)(DG)(DT) (DG)(DT)(DG)(DC)(DA)(DT)(DG)(DT)(DG)(DT) (DG) (DT)(DG)(DA)(DC)(DT)(DA)(DT)(DG) (DT)(DG)(DC)(DG)(DC)(DA)(DT)(DG)(DC)(DA) (DT)(DG) (DT)(DG)(DC)(DA)(DT)(DG)(DT) (DG)(DT)(DG)(DT)(DG)(DC)(DA)(DT)(DA)(DT) (DA)(DC)(DG) (DT)(DG)(DT)(DG)(DT)(DG) (DC)(DA)(DT)(DG)(DC)(DA)(DT)(DG)(DT)(DG) (DC)(DA)(DT)(DA) (DT)(DA)(DT)(DG)(DT) (DG)(DT)(DG)(DC)(DA)(DC)(DG)(DT)(DG)(DT) (DG)(DT)(DG)(DT)(DG) (DC)(DA)(DT)(DG) (DT)(DG)(DT)(DG)(DT)(DG)(DT)(DA)(DT)(DG) (DT)(DG)(DT)(DA)(DT)(DA) (DT)(DA)(DT) (DT)(DA)(DA)(DC)(DC)(DT)(DG)(DT)(DG)(DT) (DG)(DC)(DA)(DT)(DT)(DG)(DT) (DG)(DT) (DG)(DC)(DA)(DT)(DA)(DT)(DA)(DT)(DT)(DA) (DG)(DC)(DA)(DT)(DG)(DT)(DG)(DT) (DG) (DC)(DA)(DT)(DG)(DT) |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.2 mg/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7.5 Component:
Details: 50 mM HEPES pH 7.5, 1 mM DTT | |||||||||
Grid | Model: Quantifoil / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 4000 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |