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- EMDB-17155: Cryo-EM structure of CLOCK-BMAL1 bound to a nucleosomal E-box at ... -
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Basic information
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Title | Cryo-EM structure of CLOCK-BMAL1 bound to a nucleosomal E-box at position SHL-6.2 (DNA conformation 1) | ||||||||||||||||||
![]() | Local resolution filtered map. | ||||||||||||||||||
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![]() | E-box / transcription factor / circadian clock / GENE REGULATION | ||||||||||||||||||
Function / homology | ![]() CLOCK-BMAL transcription complex / positive regulation of skeletal muscle cell differentiation / regulation of hair cycle / NPAS4 regulates expression of target genes / positive regulation of protein acetylation / negative regulation of glucocorticoid receptor signaling pathway / maternal process involved in parturition / regulation of type B pancreatic cell development / bHLH transcription factor binding / regulation of cellular senescence ...CLOCK-BMAL transcription complex / positive regulation of skeletal muscle cell differentiation / regulation of hair cycle / NPAS4 regulates expression of target genes / positive regulation of protein acetylation / negative regulation of glucocorticoid receptor signaling pathway / maternal process involved in parturition / regulation of type B pancreatic cell development / bHLH transcription factor binding / regulation of cellular senescence / perichromatin fibrils / aryl hydrocarbon receptor complex / chromatoid body / positive regulation of circadian rhythm / negative regulation of TOR signaling / oxidative stress-induced premature senescence / negative regulation of cold-induced thermogenesis / response to redox state / negative regulation of fat cell differentiation / protein acetylation / regulation of protein catabolic process / E-box binding / regulation of insulin secretion / regulation of neurogenesis / negative regulation of tumor necrosis factor-mediated signaling pathway / 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 / epigenetic regulation of gene expression / Packaging Of Telomere Ends / histone acetyltransferase activity / 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 / nucleosomal DNA binding / histone acetyltransferase / 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 / innate immune response in mucosa / PRC2 methylates histones and DNA / DNA damage checkpoint signaling / Defective pyroptosis / HDACs deacetylate histones / cellular response to ionizing radiation / RNA Polymerase I Promoter Escape / lipopolysaccharide binding / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / 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 / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / HDMs demethylate histones / regulation of circadian rhythm / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / chromatin DNA binding / PKMTs methylate histone lysines / PML body / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / autophagy / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / positive regulation of inflammatory response / circadian rhythm / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / protein import into nucleus / UCH proteinases / nucleosome / nucleosome assembly / positive regulation of canonical Wnt signaling pathway / 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 / positive regulation of NF-kappaB transcription factor activity / Factors involved in megakaryocyte development and platelet production Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.2 Å | ||||||||||||||||||
![]() | Michael AK / Stoos L / Kempf G / Cavadini S / Thoma NH | ||||||||||||||||||
Funding support | European Union, ![]() ![]()
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![]() | ![]() Title: Cooperation between bHLH transcription factors and histones for DNA access. Authors: Alicia K Michael / Lisa Stoos / Priya Crosby / Nikolas Eggers / Xinyu Y Nie / Kristina Makasheva / Martina Minnich / Kelly L Healy / Joscha Weiss / Georg Kempf / Simone Cavadini / Lukas ...Authors: Alicia K Michael / Lisa Stoos / Priya Crosby / Nikolas Eggers / Xinyu Y Nie / Kristina Makasheva / Martina Minnich / Kelly L Healy / Joscha Weiss / Georg Kempf / Simone Cavadini / Lukas Kater / Jan Seebacher / Luca Vecchia / Deyasini Chakraborty / Luke Isbel / Ralph S Grand / Florian Andersch / Jennifer L Fribourgh / Dirk Schübeler / Johannes Zuber / Andrew C Liu / Peter B Becker / Beat Fierz / Carrie L Partch / Jerome S Menet / Nicolas H Thomä / ![]() ![]() ![]() ![]() Abstract: The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members. Here we investigate how chromatinized E-boxes are engaged ...The basic helix-loop-helix (bHLH) family of transcription factors recognizes DNA motifs known as E-boxes (CANNTG) and includes 108 members. Here we investigate how chromatinized E-boxes are engaged by two structurally diverse bHLH proteins: the proto-oncogene MYC-MAX and the circadian transcription factor CLOCK-BMAL1 (refs. ). Both transcription factors bind to E-boxes preferentially near the nucleosomal entry-exit sites. Structural studies with engineered or native nucleosome sequences show that MYC-MAX or CLOCK-BMAL1 triggers the release of DNA from histones to gain access. Atop the H2A-H2B acidic patch, the CLOCK-BMAL1 Per-Arnt-Sim (PAS) dimerization domains engage the histone octamer disc. Binding of tandem E-boxes at endogenous DNA sequences occurs through direct interactions between two CLOCK-BMAL1 protomers and histones and is important for circadian cycling. At internal E-boxes, the MYC-MAX leucine zipper can also interact with histones H2B and H3, and its binding is indirectly enhanced by OCT4 elsewhere on the nucleosome. The nucleosomal E-box position and the type of bHLH dimerization domain jointly determine the histone contact, the affinity and the degree of competition and cooperativity with other nucleosome-bound factors. | ||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 113.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.3 KB 29.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.8 KB | Display | ![]() |
Images | ![]() | 71.8 KB | ||
Others | ![]() ![]() ![]() | 136.1 MB 136.2 MB 136.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1022.4 KB | Display | ![]() |
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Full document | ![]() | 1022 KB | Display | |
Data in XML | ![]() | 20 KB | Display | |
Data in CIF | ![]() | 26.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8osjMC ![]() 8oskC ![]() 8oslC ![]() 8otsC ![]() 8ottC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 | Local resolution filtered map. | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.68 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Unfiltered map.
File | emd_17155_additional_1.map | ||||||||||||
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Annotation | Unfiltered map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map B.
File | emd_17155_half_map_1.map | ||||||||||||
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Annotation | Half-map B. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map A.
File | emd_17155_half_map_2.map | ||||||||||||
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Annotation | Half-map A. | ||||||||||||
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Density Histograms |
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Sample components
+Entire : CLOCK-BMAL1 bound to a nucleosome at SHL -6.2
+Supramolecule #1: CLOCK-BMAL1 bound to a nucleosome at SHL -6.2
+Supramolecule #2: Nucleosome core particle
+Supramolecule #3: Histone octamer
+Supramolecule #4: Nucleosomal DNA
+Supramolecule #5: CLOCK-BMAL1 heterodimer
+Macromolecule #1: Histone H3.1
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1-B/E
+Macromolecule #4: Histone H2B type 1-J
+Macromolecule #7: Circadian locomoter output cycles protein kaput
+Macromolecule #8: Basic helix-loop-helix ARNT-like protein 1
+Macromolecule #5: DNA (124-MER)
+Macromolecule #6: DNA (124-MER)
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |