The synthesis of pre-mRNA by RNA polymerase II (Pol II) involves the formation of a transcription initiation complex and a transition to an elongation complex 1–4.The large subunit of Pol II contains an intrinsically disordered C-terminal domain (CTD), which is phosphorylated by cyclin-dependent kinases (CDKs) during the initiation-to-elongation …
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, and Richard A. Young. +18 authors. Authors Info & Affiliations. Science. 21 Jun 2018. Vol 361, Issue 6400. DOI: 10.1126/science.aar3958. …
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Lu, H. et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature 558, 318–323 (2018). Article ADS CAS Google Scholar
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Transcription Factors Activate Genes through Phase-Separation Capacity of their Activation Domains Boija, A., Klein, I.A., Sabari, B., Dall'Agnese, A., Coffey, E.L ...
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that the assembly of biomolecules at active super-enhancers is due to phase separation of the apparatus at these elements. Experimental analysis subsequently showed that transcription factors, cofactors and RNA polymerase II do form dynamic, transcriptionally active biomolecular ... Richard Young Created Date:
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We recently provided experimental evidence that super-enhancers and their components do form phase-separated condensates (Sabari et al., 2018; Boija et al., 2018), establishing …
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Signal-dependent incorporation of signaling factors into condensates at super-enhancers. Recent studies have shown that TFs and Mediator form phase-separated condensates at super-enhancers (Boija et al., 2018; Cho et al., 2018; Sabari et al., 2018) and the terminal signaling factors of the WNT, JAK/STAT and TGF-β pathways (β …
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We show that the embryonic stem cell (ESC) pluripotency TF OCT4, the estrogen receptor (ER), and the yeast TF GCN4 form phase-separated condensates …
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Phase separation of fluids is a physicochemical process by which molecules separate into a dense phase and a dilute phase. Phase-separated biomolecular condensates, which include the nucleolus, nuclear speckles, stress granules, and others, provide a mechanism to compartmentalize and concentrate biochemical reactions within …
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Methyl CpG binding protein 2 (MeCP2) is a key component of constitutive heterochromatin, which is crucial for chromosome maintenance and transcriptional silencing 1-3.Mutations in the MECP2 gene cause the progressive neurodevelopmental disorder Rett syndrome 3-5, which is associated with severe mental disability and autism-like symptoms that affect …
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Focus on phase separation. Phase separation (PS) refers to the de-mixing process of a homogenous phase to form dense and dilute phases, which is explored in this collection of recent articles from ...
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Phase separation underlies the formation of subcompartments both at the pre- and post-synapse, such as SV clusters [ 23, 24 ], active zone proteins [ 25, 26 ], endocytic sites [ 27, 28 ], and postsynaptic densities in both excitatory and inhibitory post synapses [ 29, 30] ( Figure 2 ).
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MegaTrans enhancer proteins form phase-separated liquid droplets. Estrogen signaling activates 7,000–8,000 enhancers genome-wide, out of which 1,248 are exceptionally active, on the basis of ...
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For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation …
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The histidine-rich domain of cyclin T1 promotes phase separation into liquid droplets, which facilitates the hyperphosphorylation of the C-terminal domain repeats of RNA polymerase II.
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Phase separation plays an important regulatory role in the process of mRNA transcription regulation. Richard A. Young first proposed the hypothesis that phase separation regulated RNA transcription in 2017 [69].Nowadays, phase separation has become a new interpretation mechanism of transcription regulation.
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The phase separation may rev up a molecular process that normally ticks over barely above idle, the researchers proposed. And work from geneticist Richard Young's lab at the Massachusetts Institute of Technology suggests that phase separation concentrates droplets of proteins needed to turn on the activity of genes or prod a chromosome to ...
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For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with …
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Richard A. Young. Three properties of enhancer clusters led us to call them super-enhancers. ... Although phase separation of TFs at enhancers presents an interesting model to explain enhancer ...
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Evidence from in vitro and in vivo experiments support a model where RNAs produced during early steps in transcription initiation stimulate condensate formation, whereas the burst of RNAs produced during elongation stimulate condensate dissolution. We propose that transcriptional regulation incorporates a feedback mechanism whereby …
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Phase separation directs ubiquitination of gene-body nucleosomes. The yeast E3 ligase Bre1 forms a core–shell condensate with the scaffold protein Lge1, implicating liquid–liquid phase ...
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TF-Coactivator phase separation is dependent on residues required for transactivation. ... information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact Richard Young (ude.tim.iw@gnuoy). EXPERIMENTAL MODEL AND SUBJECT DETAILS. Cells .
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Richard A. Young. Nature Chemical Biology 18, 1298–1306 ( 2022) Cite this article. 9128 Accesses. 44 Citations. 29 Altmetric. Metrics. Abstract. Biomolecular …
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Abstract. The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that …
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Abstract. Phase-separated multi-molecular assemblies provide a general regulatory mechanism to compartmentalize biochemical reactions within cells. We propose that a phase separation model explains established and recently described features of transcriptional control. These features include the formation of super-enhancers, the …
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Abstract. Phase separation is the basis for the formation of membrane-less organelles in cells and is involved in many biological processes. Many biological macromolecules, such as proteins and nucleic acids, exert their biological functions by forming phase-separated condensates, and phase separation is closely related to …
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Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary to understand the consequences of liquid-like states for biological functions.
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Many cellular proteins demix spontaneously from solution to form liquid condensates. These phase-separated structures have wide-ranging roles in health and disease. Elucidating the molecular driving forces underlying liquid-liquid phase separation (LLPS) is therefore a key objective for understanding biological function and malfunction. …
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Indeed, work from Richard Young's laboratory revealed that while the hypophosphorylated CTD of Pol II is incorporated into Mediator condensates, ... Phase separation has been closely observed in many of these procedures. The influenza virus RNA and ribonucleoproteins pack and form cellular condensates upon entry into the …
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Leading Edge Perspective A Phase Separation Model for Transcriptional Control Denes Hnisz,1,10 Krishna Shrinivas,2,7,8,10 Richard A. Young,1,3,* Arup K. Chakraborty,2,4,5,6,7,8,* and Phillip A. Sharp3,9,* 1Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA 2Department of Chemical …
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Richard A. Young. Arup K. Chakraborty. Phillip A. Sharp. Show footnotes. Open Archive DOI: https://doi/10.1016/j.cell.2017.02.007. A Phase …
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Postdocs from Whitehead Institute Member Richard A. Young's lab found that imaging and molecular manipulation reveal how biomolecular condensates form and offer clues to the …
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Rick Young is a pioneer in the systems biology of gene control and expression and has harnessed the emergent understanding of biomolecular condensates and phase separation for new insights in his field. He is a member of the Whitehead Institute and Professor of Biology at the Massachusetts Institute of Technology.
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