Yawen Bai

National Institutes of Health, 베서스다, Maryland, United States

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Publications (72)523.42 Total impact


  • No preview · Conference Paper · Oct 2015
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    Full-text · Dataset · Aug 2015
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    ABSTRACT: Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the struc- tural basis of nucleosome recognition by linker his- tones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 A ̊ resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach ex- periments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures.
    Full-text · Article · Aug 2015 · Molecular cell
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    ABSTRACT: Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures. Copyright © 2015 Elsevier Inc. All rights reserved.
    Preview · Article · May 2015 · Journal of biomolecular Structure & Dynamics
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    ABSTRACT: The p53 tumor suppressor is a critical mediator of the cellular response to stress. The N-terminal transactivation domain of p53 makes protein interactions that promote its function as a transcription factor. Among those cofactors is the histone acetyltransferase p300, which both stabilizes p53 and promotes local chromatin unwinding. Here, we report the NMR solution structure of the Taz2 domain of p300 bound to the second transactivation subdomain of p53. In the complex, p53 forms an α-helix between residues 47-55 that interacts with the α1- α2- α3 face of Taz2. Mutational analysis indicated several residues in both p53 and Taz2 that are critical for stabilizing the interaction. Finally, further characterization of the complex by isothermal titration calorimetry revealed that complex formation is pH-dependent and releases a bound chloride ion. This study highlights differences in the structures of complexes formed by the two transactivation subdomains of p53 which may be broadly observed and play critical roles for p53 transcriptional activity.
    No preview · Article · Mar 2015 · Biochemistry
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    ABSTRACT: Macromolecular complexes of protein and DNA are often resolved in a low resolution structure (3.0 angstroms or lower). Because nucleic acids suffer radiation damage more than amino acids, the resulting temperature factors for DNA are generally higher than those for protein. Recognition of DNA-specific interactions with protein is a challenge at low resolution. The use of low-resolution refinement ([1]) or the reference high resolution model could improve DNA densities. A number of DNA/protein and nucleosome complexes (i.e. RAGE-DNA [2], CENP-C-NCP[3]) that we have recently refined demonstrated the validation of these methods. [1] Brunger AT, Adams PD, Fromme P, et al. " Improving the accuracy of macromolecular structure refinement at 7 angstroms resolution ". Structure, 20:957-966, 2012, [2] Sirois C, Jin T, Miller AL, et al. " RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA
    Full-text · Article · Aug 2014 · Acta crystallographica. Section A, Foundations of crystallography
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    Dataset: mmc1

    Full-text · Dataset · Feb 2014
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    ABSTRACT: Histone variant H2A.Z-containing nucleosomes exist at most eukaryotic promoters and play important roles in gene transcription and genome stability. The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. How SWR1 catalyzes the replacement reaction is largely unknown. Here, we determined the crystal structure of the N-terminal region (599-627) of the catalytic subunit Swr1, termed Swr1-Z domain, in complex with the H2A.Z-H2B dimer at 1.78 Å resolution. The Swr1-Z domain forms a 310 helix and an irregular chain. A conserved LxxLF motif in the Swr1-Z 310 helix specifically recognizes the αC helix of H2A.Z. Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.
    Full-text · Article · Feb 2014 · Molecular cell
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    Full-text · Dataset · Feb 2014
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    ABSTRACT: Linker H1 histones facilitate formation of higher-order chromatin structures and play important roles in various cell functions. Despite several decades of effort, the structural basis of how H1 interacts with the nucleosome remains elusive. Here, we investigated Drosophila H1 in complex with the nucleosome, using solution nuclear magnetic resonance spectroscopy and other biophysical methods. We found that the globular domain of H1 bridges the nucleosome core and one 10-base pair linker DNA asymmetrically, with its α3 helix facing the nucleosomal DNA near the dyad axis. Two short regions in the C-terminal tail of H1 and the C-terminal tail of one of the two H2A histones are also involved in the formation of the H1-nucleosome complex. Our results lead to a residue-specific structural model for the globular domain of the Drosophila H1 in complex with the nucleosome, which is different from all previous experiment-based models and has implications for chromatin dynamics in vivo.
    Full-text · Article · Nov 2013 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Comment on: Kato H, et al. Science 2013; 340:1110-3.
    Full-text · Article · Sep 2013 · Cell cycle (Georgetown, Tex.)
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    ABSTRACT: Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.
    Full-text · Article · May 2013 · Science
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    ABSTRACT: In eukaryotes, a variant of conventional histone H3 termed CenH3 epigenetically marks the centromere. The conserved CenH3 chaperone specifically recognizes CenH3 and is required for CenH3 deposition at the centromere. Recently, the structures of the chaperone/CenH3/H4 complexes have been determined for Homo sapiens (Hs) and the budding yeasts Saccharomyces cerevisiae (Sc) and Kluyveromyces lactis (Kl). Surprisingly, the three structures are very different, leading to different proposed structural bases for chaperone function. The question of which structural region of CenH3 provides the specificity determinant for the chaperone recognition is not fully answered. Here, we investigated these issues using solution NMR and site-directed mutagenesis. We discovered that, in contrast to previous findings, the structures of the Kl and Sc chaperone/CenH3/H4 complexes are actually very similar. This new finding reveals that both budding yeast and human chaperones use a similar structural region to block DNA from binding to the histones. Our mutational analyses further indicate that the N-terminal region of the CenH3 α2 helix is sufficient for specific recognition by the chaperone for both budding yeast and human. Thus, our studies have identified conserved structural bases of how the chaperones recognize CenH3 and perform the chaperone function.
    Full-text · Article · Jan 2013 · Journal of Molecular Biology
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    Full-text · Dataset · Dec 2012
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    Full-text · Dataset · Dec 2012
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    ABSTRACT: In eukaryotes, a variant of conventional histone H3 termed CenH3 epigenetically marks the centromere. The conserved CenH3chaperone specifically recognizes CenH3 and is required for CenH3 deposition at the centromere. Recently, the structures of the chaperone/CenH3/H4 complexes have been determined for H. sapiens (Hs) andthe budding yeastsS. cerevisiae (Sc) and K. lactis (Kl). Surprisingly, the three structures arevery different, leading to different proposed structural bases for chaperone function.The question of which structural region of CenH3 providesthe specificity determinant for the chaperone recognition is not fully answered.Here, we investigated these issues usingsolution NMR and site-directed mutagenesis. We discovered that, in contrast to previous findings, the structures of the Kland Sc chaperone/CenH3/H4 complexes are actually very similar. This new finding reveals that both budding yeast and human chaperones use a similar structural region to block DNA from binding to the histones. Our mutational analyses further indicate that the N-terminal region of the CenH3α2 helix is sufficient for specific recognition by the chaperone for both budding yeast and human. Thus, our studies have identifiedconserved structural bases of how the chaperonesrecognize CenH3 and perform the chaperone function.
    Full-text · Article · Nov 2012 · Journal of Molecular Biology
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    ABSTRACT: Histone tails and their posttranslational modifications play important roles in regulating the structure and dynamics of chromatin. For histone H4, the basic patch K(16)R(17)H(18)R(19) in the N-terminal tail modulates chromatin compaction and nucleosome sliding catalyzed by ATP-dependent ISWI chromatin remodeling enzymes while acetylation of H4 K16 affects both functions. The structural basis for the effects of this acetylation is unknown. Here, we investigated the conformation of histone tails in the nucleosome by solution NMR. We found that backbone amides of the N-terminal tails of histones H2A, H2B, and H3 are largely observable due to their conformational disorder. However, only residues 1-15 in H4 can be detected, indicating that residues 16-22 in the tails of both H4 histones fold onto the nucleosome core. Surprisingly, we found that K16Q mutation in H4, a mimic of K16 acetylation, leads to a structural disorder of the basic patch. Thus, our study suggests that the folded structure of the H4 basic patch in the nucleosome is important for chromatin compaction and nucleosome remodeling by ISWI enzymes while K16 acetylation affects both functions by causing structural disorder of the basic patch K(16)R(17)H(18)R(19).
    Full-text · Article · May 2012 · Journal of Molecular Biology
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    ABSTRACT: Comment on: Zhou et al. Nature 2011; 47:234-237, Hu et al. Genes Dev 2011; 25:901-6 and Cho et al. Proc Natl Acad Sci USA 2011; 108:9367-71.
    Full-text · Article · Oct 2011 · Cell cycle (Georgetown, Tex.)
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    Full-text · Article · Aug 2011 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Chromatin structure and function are regulated by numerous proteins through specific binding to nucleosomes. The structural basis of many of these interactions is unknown, as in the case of the high mobility group nucleosomal (HMGN) protein family that regulates various chromatin functions, including transcription. Here, we report the architecture of the HMGN2-nucleosome complex determined by a combination of methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal DNA near the entry/exit point, "stapling" the histone core and the DNA. These results provide insight into how HMGNs regulate chromatin structure through interfering with the binding of linker histone H1 to the nucleosome as well as a structural basis of how phosphorylation induces dissociation of HMGNs from chromatin during mitosis. Importantly, our approach is generally applicable to the study of nucleosome-binding interactions in chromatin.
    Full-text · Article · Jul 2011 · Proceedings of the National Academy of Sciences

Publication Stats

4k Citations
523.42 Total Impact Points

Institutions

  • 2002-2015
    • National Institutes of Health
      • • Laboratory of Biochemistry and Molecular Biology
      • • Chemical Biology Laboratory
      베서스다, Maryland, United States
  • 1999-2015
    • National Cancer Institute (USA)
      • • Laboratory of Biochemistry and Molecular Biology
      • • Center for Cancer Research
      • • Chemical Biology Laboratory
      베서스다, Maryland, United States
  • 2006-2013
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2010
    • Philadelphia University
      Philadelphia, Pennsylvania, United States
  • 2002-2006
    • Northern Inyo Hospital
      BIH, California, United States
  • 1996-2001
    • The Scripps Research Institute
      • • Skaggs Institute for Chemical Biology
      • • Department of Cell and Molecular Biology
      لا هویا, California, United States
  • 1993-1994
    • University of Pennsylvania
      • Department of Biochemistry and Biophysics
      Philadelphia, Pennsylvania, United States