Publications by authors named "Moritz Ochmann"

2 Publications

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Structural basis of nucleosome transcription mediated by Chd1 and FACT.

Nat Struct Mol Biol 2021 Apr 12;28(4):382-387. Epub 2021 Apr 12.

Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany.

Efficient transcription of RNA polymerase II (Pol II) through nucleosomes requires the help of various factors. Here we show biochemically that Pol II transcription through a nucleosome is facilitated by the chromatin remodeler Chd1 and the histone chaperone FACT when the elongation factors Spt4/5 and TFIIS are present. We report cryo-EM structures of transcribing Saccharomyces cerevisiae Pol II-Spt4/5-nucleosome complexes with bound Chd1 or FACT. In the first structure, Pol II transcription exposes the proximal histone H2A-H2B dimer that is bound by Spt5. Pol II has also released the inhibitory DNA-binding region of Chd1 that is poised to pump DNA toward Pol II. In the second structure, Pol II has generated a partially unraveled nucleosome that binds FACT, which excludes Chd1 and Spt5. These results suggest that Pol II progression through a nucleosome activates Chd1, enables FACT binding and eventually triggers transfer of FACT together with histones to upstream DNA.
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http://dx.doi.org/10.1038/s41594-021-00578-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046669PMC
April 2021

Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations.

Elife 2020 06 16;9. Epub 2020 Jun 16.

Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany.

Chromatin remodeling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodeling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here, we report the cryo-electron microscopy (cryo-EM) structure of CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodeling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.
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http://dx.doi.org/10.7554/eLife.56178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338049PMC
June 2020