ORCID Profile
0000-0001-5136-5331
Current Organisation
University of Colorado at Boulder
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Epigenetics (incl. genome methylation and epigenomics) | Structural biology (incl. macromolecular modelling) | Genetics | Genome structure and regulation
Publisher: Informa UK Limited
Date: 09-2016
DOI: 10.1128/MCB.00195-16
Publisher: eLife Sciences Publications, Ltd
Date: 27-12-2017
DOI: 10.7554/ELIFE.33442
Abstract: Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.
Publisher: Cold Spring Harbor Laboratory
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 12-2000
DOI: 10.1038/81971
Abstract: Activation of transcription within chromatin has been correlated with the incorporation of the essential histone variant H2A.Z into nucleosomes. H2A.Z and other histone variants may establish structurally distinct chromosomal domains however, the molecular mechanism by which they function is largely unknown. Here we report the 2.6 A crystal structure of a nucleosome core particle containing the histone variant H2A.Z. The overall structure is similar to that of the previously reported 2.8 A nucleosome structure containing major histone proteins. However, distinct localized changes result in the subtle destabilization of the interaction between the (H2A.Z-H2B) dimer and the (H3-H4)(2) tetramer. Moreover, H2A.Z nucleosomes have an altered surface that includes a metal ion. This altered surface may lead to changes in higher order structure, and/or could result in the association of specific nuclear proteins with H2A.Z. Finally, incorporation of H2A.Z and H2A within the same nucleosome is unlikely, due to significant changes in the interface between the two H2A.Z-H2B dimers.
Publisher: EMBO
Date: 12-10-2015
Publisher: Wiley
Date: 15-06-2018
DOI: 10.1111/FEBS.14495
Abstract: How did the nucleosome, the fundamental building block of all eukaryotic chromatin, evolve? This central question has been impossible to address because the four core histones that make up the protein core of the nucleosome are so highly conserved in all eukaryotes. With the discovery of small, minimalist histone-like proteins in most known archaea, the likely origin of histones was identified. We recently determined the structure of an archaeal histone-DNA complex, revealing that archaeal DNA topology and protein-DNA interactions are astonishingly similar compared to the eukaryotic nucleosome. This was surprising since most archaeal histones form homodimers which consist only of the minimal histone fold and are devoid of histone tails and extensions. Unlike eukaryotic H2A-H2B and H3-H4 heterodimers that assemble into octameric particles wrapping ~ 150 bp DNA, archaeal histones form polymers around which DNA coils in a quasi-continuous superhelix. At any given point, this superhelix has the same geometry as nucleosomal DNA. This suggests that the architectural role of histones (i.e. the ability to bend DNA into a nucleosomal superhelix) was established before archaea and eukaryotes erged, while the ability to form discrete particles, together with signaling functions of eukaryotic chromatin (i.e. epigenetic modifications) were secondary additions.
Publisher: Informa UK Limited
Date: 04-2016
DOI: 10.1128/MCB.00835-15
Publisher: Elsevier BV
Date: 09-2013
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.MOLCEL.2004.10.023
Abstract: Controlling the degree of higher order chromatin folding is a key element in partitioning the metazoan genome into functionally distinct chromosomal domains. However, the mechanism of this fundamental process is poorly understood. Our recent studies suggested that the essential histone variant H2A.Z and the silencing protein HP1alpha may function together to establish a specialized conformation at constitutive heterochromatic domains. We demonstrate here that HP1alpha is a unique chromatin binding protein. It prefers to bind to condensed higher order chromatin structures and alters the chromatin-folding pathway in a novel way to locally compact in idual chromatin fibers without crosslinking them. Strikingly, both of these features are enhanced by an altered nucleosomal surface created by H2A.Z (the acidic patch). This shows that the surface of the nucleosome can regulate the formation of distinct higher order chromatin structures mediated by an architectural chromatin binding protein.
Publisher: Wiley
Date: 15-07-2004
Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-08-2017
Publisher: Elsevier BV
Date: 12-2011
Publisher: Elsevier BV
Date: 06-2004
Publisher: Public Library of Science (PLoS)
Date: 21-05-2015
Publisher: Springer Science and Business Media LLC
Date: 19-02-2002
DOI: 10.1038/NSB767
Publisher: Oxford University Press (OUP)
Date: 24-11-2011
DOI: 10.1093/NAR/GKR1045
Publisher: Springer Science and Business Media LLC
Date: 22-06-2012
DOI: 10.1038/NRM3382
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.CELL.2009.06.037
Abstract: The properties of centromeric nucleosomes have been the subject of considerable debate and controversy. Furuyama and Henikoff (2009) now provide surprising evidence that centromeric nucleosomes wrap DNA in an orientation that is opposite to that of canonical nucleosomes.
Start Date: 2023
End Date: 12-2025
Amount: $772,621.00
Funder: Australian Research Council
View Funded Activity