4DCellFate

Developing a global understanding of the PRC and NuRD complexes in stem cell differentiation and in disease

Review by O'Shaughnessy and Hendrich that describes that CHD4 is a defining member of the NuRD complex, but evidence is accumulating that CHD4 also plays important NuRD-independent roles in the DNA-damage response and cell cycle progression, as well as in transcriptional regulation.

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Here, the Berger group highlights recent major achievements in multiprotein complex structure research that were catalyzed by this versatile recombinant complex expression tool.

In mice, Hdac1 is shown to act distinctly depending on the tumor stage: it works as an oncosuppressor during initiation but as an oncogene during maintenance.

Here, Park and Lehner propose that the tight regulation of epistatic interaction network hubs is critical for maintaining a robust phenotype.

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A timely review from the Schaffitzel lab about recent accomplishments and limitations of purifying large, endogenous macromolecular machines.

Brian Hendrich and coworkers review the evidence for the presence of repressors at actively transcribed regions and assess what roles they might be playing. They propose that the modulation of expression levels by chromatin-modifying, co-repressor complexes provides transcriptional fine-tuning that drives development.

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Lluis Morey, Luigi Aloia, Luciano Di Croce, and coworkers analyzed 2.64 billion DNA nucleotides of DNA from mouse embryonic stem cells to determine which regions are controlled by PRC1-RYBP as compared to PRC1-CBX7.

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Until now, the inability to produce enough high-quality recombinant complex has hindered scientists from obtaining the structural information necessary to fully understand the molecular function of the general transcription factor TFIID. Several groups led by the Berger team have now elucidated a high-resolution structure (11.6Å) for the core TFIID complex, a 650 kDa complex containing ten protein subunits. Their findings, published in Nature, now reveal the architecture of the core TFIID and answer several long-standing questions about TFIID.

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In this review, Lehner highlights some recent work in model organisms that is relevant to the problem of making accurate phenotypic predictions in individual humans and discusses the challenges that remain.

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In this manuscript from the Vermeulen lab, the stoichiometry of the epigenetic regulator complexes of MBD3/NuRD and PRC2 were determined using the novel iBAC system of label-free, quantitative mass spectrometry–based proteomics.

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