821 research outputs found
Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations
No full textChromatin remodelling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodelling 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 Homo sapiens 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 remodelling. 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
Structural basis of nucleosome transcription mediated by Chd1 and FACT
No full textEfficient 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
Kosciusko [music] /
No full textFor voice and piano.; Cover title.; "Introduced & sung by Miss Nella Webb."; Cover carries portraits of Nella Webb (by Rudolph Buchner), Charles Vaude and Moritz Lutzen.; Words printed as text on p. [4].; "During Moritz Lutzen's visit to Australia he offered a prize for the best lyric, by an Australian author to be set to music by himself. The prize was awarded to Charles Vaude, for his lyric 'Kosciusko,' and Miss Nella Webb produced this song with instantaneous success."--P. [4].; Also available online http://nla.gov.au/nla.mus-an8393500; 1913, by Victor J. Draper, Sydney.; NLA's NL copy from the collection of Keith Watson. ANL
Structure of a backtracked hexasomal intermediate of nucleosome transcription
No full textDuring gene transcription, RNA polymerase II (RNA Pol II) passes nucleosomes with the help of various elongation factors. Here, we show that RNA Pol II achieves efficient nucleosome passage when the human elongation factors DSIF, PAF1 complex (PAF), RTF1, SPT6, and TFIIS are present. The cryo-EM structure of an intermediate of the nucleosome passage shows a partially unraveled hexasome that lacks the proximal H2A-H2B dimer and interacts with the RNA Pol II jaw, DSIF, and the CTR9trestle helix. RNA Pol II adopts a backtracked state with the RNA 3' end dislodged from the active site and bound in the RNA Pol II pore. Additional structures and biochemical data show that human TFIIS enters the RNA Pol II pore and stimulates the cleavage of the backtracked RNA and nucleosome passage
Structural basis of Integrator-dependent RNA polymerase II termination
No full textAbstract
The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript
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, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator–PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10–INTS13–INTS14–INTS15 module that may use its ‘sting’ to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator–PP2A complex in an inactive closed conformation
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reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements
Letter containing inquiry regarding the ethnic identity of the descendents of Georg Moritz Oppenheim.
No full textLetter from Wilhelm Gehlig to Rabbi Dr. Freudenthal in Nuremberg with a genealogical question regarding Georg Moritz Oppenheim. Of particular interest to the author is to determine whether Oppenheim's descendents are "rein jüdischen Blutes (=of pure Jewish blood)."Robert Singermandigitize
Molecular mechanism of co-transcriptional H3K36 methylation by SETD2
No full textAbstract H3K36me3 is a hallmark of actively and recently transcribed genes and contributes to cellular memory and identity. The deposition of H3K36me3 occurs co-transcriptionally when the methyltransferase SETD2 associates with RNA polymerase II. Here we present three cryo-EM structures of SETD2 bound to RNA polymerase II elongation complexes at different states of nucleosome passage. Together with functional probing, our results suggest a 3-step mechanism of transcription-coupled H3K36me3 deposition. First, binding to the elongation factor SPT6 tethers the catalytic SET domain in proximity to the upstream DNA. Second, RNA polymerase II nucleosome passage leads to the transfer of a hexasome from downstream to upstream, poised for methylation. Finally, continued transcription leads to upstream nucleosome reassembly, partial dissociation of the histone chaperone FACT and sequential methylation of both H3 tails, completing H3K36me3 deposition of an upstream nucleosome after RNA polymerase II passage
Conventional and circular economy compliant modification strategies for recycled polypropylene
No full textAuthor Moritz MagerMasterarbeit Universität Linz 2021Arbeit gesperr
Conventional and circular economy compliant modification strategies for recycled polypropylene
No full textAuthor Moritz MagerMasterarbeit Universität Linz 2021Arbeit gesperr
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