Publications

For a full publication list, please see the links on side bar.

Recent key publications

• Chaperoning of the histone octamer by the acidic domain of DNA repair factor APLF
  I. Corbeski*, X. Guo*, B.V. Eckhardt, D. Fasci, W. Wiegant, M.A. Graewert, K. Vreeken, H. Wienk, D.I. Svergun, A.J.R. Heck, H. van Attikum, R. Boelens, T.K. Sixma, F. Mattiroli and H. van Ingen (2022). Sci. Adv. DNA damage repair requires manipulation of chromatin involving first nucleosome disassembly and later chromatin restoration.
  We show that the initrinsically disordered chaperone domain of repair factor APLF can single-handedly assembly the histone octamer and transfer it to DNA to form nucleosomes. While histone chaperones are generally specific for either H2A-H2B or H3-H4 histones, this work is the first high-resolution characterization of a chaperone that can bind all four histones. The structure of the APLF acidic domain-histone complex explains how APLF can assemble the histones in their nucleosomal configuration and transfer them to DNA. This work was a great collaboration with the Heck, Svergun, van Attikum, Sixma and Mattiroli groups!.
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• NMR-driven integrative structure of the RNF168-nucleosome complex explains Ub specificity
  V. Horn*, M. Uckelmann*, H. Zhang, J. Eerland, I. Aarsman, U.B. le Paige, C. Davidovich, T.K. Sixma and H. van Ingen (2019). Nat. Commun.
  Ubiquitination of H2A K13/K15 is an important regulatory signal in control of DNA damage repair.
  The E3 enzyme RNF168 controls the specificity of this reaction, making sure only K13/15 in H2A get ubiuitinated.
  We used NMR, mutagenesis and cross-linking mass-spectrometry to get an insightful integrative structure,
  that show in deatil how anchoring of the RNF168 to the nucleosome acidic patch position the E2~Ub above the targeted lysines.
  This work was a collaboration with the Sixma group at the Netherlands Cancer Institute.
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  PDB-DEV

• Unspinning chromatin
  C.L.van Emmerik and H. van Ingen (2019). Prog. NMR Spectr.
  A comprehensive review of NMR on the nucleosome from the 1960s till the present day…
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• Site-specific studies of nucleosome interactions by solid-state NMR spectroscopy
  S. Xi*, U.B. le Paige*, M. Baldus, and H. van Ingen (2018). Angew. Chem. Int. Ed. Engl.
  Spinning down nucleosomes to pin down interactions…
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Latest

• How acidic is the nucleosome acidic patch? H. Zhang, J. Eerland, V. Horn, R. Schellevis, H. van Ingen (2021) Sci Rep. We mapped the pKa of the acidic and histidines residues in and around the acidic patch using NMR. Our data show that at slightly acidic pH, protonation of H106, H46 in H2B and D89 in H2A will reduce electronegativity. This will be important o understand the impact of pH changes on nucleosome-protein interactions in vitro, in silico or in vivo. Read the paper

• Beyond the nucleosome
  V.R. Lobbia, M.C. Trueba Sanchez, H. van Ingen (2021). J. Mol. Biol.
  The structure-function relationship of chromatin is a complex, multi-scale problem.
  In this review, we examined the interplay between higher-order chromatin structure and nucleosome-nucleosome and nucleosome-protein interactions.
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• Let’s roll and make nucleosomal DNA
  C.L. van Emmerik, I. Gachulincova, V.R. Lobbia, M.A. Daniëls, H.A. Heus, A. Soufi, F.H.T. Nelissen, H. van Ingen (2020). Anal. Biochem.
  We developed a flexible method to produce large quantities of genomic nucleosomal DNA, based on rolling-circle-amplification (RCA).
  This will facilitate structural studies of genomic nucleosomes by making it easier to produce the required DNA.
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• Peptide mimics nucleosome
  V.Horn, S.A.K. Jongkees, H. van Ingen (2020). Molecules
  Imitating Nature is hard! Recognition of H3K36me is hevaily influenced by the nucleosomal environment.
  We attempted to mimicking this nucleosomal context in a peptide to potentially identify new inhibitors for the readers of this modification.
  The peptides indeed have increased binding affinity but an altered mode, reducing the occupancy of the aromatic cage on the reader.
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Older key publications

• Nucleosomal DNA binding drives the recognition of H3K36 methylated nucleosomes by the PSIP1-PWWP domain
  R. van Nuland, F.M.A. van Schaik, M. Simonis, S. van Heesch, E. Cuppen, R. Boelens, M. Timmers and H. van Ingen (2013). Epigenetics & Chromatin
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• Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR
  H. Kato*,H. van Ingen*, B.-R. Zhou*, H. Feng, M. Bustin, L.E. Kay and Y. Bai (2011). Proc. Natl. Acad. Sci. USA
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• Weak coupling between magnetically inequivalent spins
  U.B. Le Paige, B. Smits,P. ‘t Hart,F. Lefeber, N.I. Martin, H. van Ingen (2017). J Magn Reson. As it turns out, our group has spent considerable time on analyzing the effects of strong coupling in NMR experiments and spectra.
  Strong coupling occurs when the J-coupling is large compared to the frequency separation and is probably best known for the roofing effect in AB-type spectra.
  While strong coupling has been studied intensively since the late 50’s, there are still fundamental and new aspects to be discovered in this fascinating corner of spectroscopy.
  In this case, we discovered a case where chemically equivalent nuclei are in fact weakly coupled, resulting a very peculiar spectrum that can be seen as both deceptively complicated or deceptively simple.
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