Richard Young Phase Separation

منتوجات جديدة

Partitioning of cancer therapeutics in nuclear condensates

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 …

منتوجات جديدة

A Phase Separation Model for Transcriptional Control

A Phase Separation Model for Transcriptional Control. Cell. 2017 Mar 23;169 (1):13-23. doi: 10.1016/j.cell.2017.02.007. Authors. Denes Hnisz 1, Krishna …

منتوجات جديدة

Transcription Factors Activate Genes through the Phase …

We show that the embryonic stem cell (ESC) pluripotency TF OCT4, the estrogen receptor (ER), and the yeast TF GCN4 form phase-separated condensates …

منتوجات جديدة

MIT Open Access Articles Testing the super-enhancer …

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:

منتوجات جديدة

Phase separation in biology

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 ...

منتوجات جديدة

Coactivator condensation at super-enhancers links phase separation …

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 …

منتوجات جديدة

Learning the chemical grammar of biomolecular condensates

Richard A. Young. Nature Chemical Biology 18, 1298–1306 ( 2022) Cite this article. 9128 Accesses. 44 Citations. 29 Altmetric. Metrics. Abstract. Biomolecular …

منتوجات جديدة

How phase separation is revolutionizing biology

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 role of phase separation in health and disease. February 27, 2024

منتوجات جديدة

MeCP2 links heterochromatin condensates and …

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 …

منتوجات جديدة

How phase separation is revolutionizing biology

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 …

منتوجات جديدة

Transcription Factors Activate Genes through the Phase …

For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation …

منتوجات جديدة

From start to end: Phase separation and transcriptional regulation

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 …

منتوجات جديدة

Phase separation in RNA biology

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 …

منتوجات جديدة

Richard A. Young Lab, Whitehead Institute/MIT

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 …

منتوجات جديدة

Drugs enter a liquid phase | Nature Reviews Molecular Cell …

A study from Young and colleagues now shows that chemical compounds can also undergo partitioning into condensates, affecting their activity in cells. The authors hypothesized that small-molecule ...

منتوجات جديدة

Transcription Factors Activate Genes through the Phase-Separation …

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 …

منتوجات جديدة

Phase-separation mechanism for C-terminal …

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.

منتوجات جديدة

Liquid-Liquid Phase Separation in Biology | Annual Reviews

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.

منتوجات جديدة

Coactivator condensation at super-enhancers links phase …

These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms …

منتوجات جديدة

Young Lab :: Publications

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 ...

منتوجات جديدة

BRD4-targeting PROTAC as a unique tool to study …

SE regions were identified using ROSE software developed by Richard A. Young 41,55. ... Lu, H. et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II.

منتوجات جديدة

Partitioning of cancer therapeutics in nuclear condensates | Science …

The five to 10 billion protein molecules of cells are compartmentalized into both membrane-bound and non–membrane-bound organelles (1–3).Many non–membrane-bound organelles are phase-separated biomolecular condensates with distinct physicochemical properties that can absorb and concentrate specific proteins and …

منتوجات جديدة

RNA and liquid-liquid phase separation

In 2017, Richard A. Young discovered that SEs can bind to high-density transcription-related proteins and RNAs, and proposed that the phase separation …

منتوجات جديدة

Leading Edge Perspective

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 …

منتوجات جديدة

A Phase Separation Model for Transcriptional Control

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 …

منتوجات جديدة

RNA in formation and regulation of transcriptional condensates

The mechanism underlying this phenomenon is nonequilibrium regulation of complex coacervation, a type of liquid–liquid phase separation mediated by electrostatic interactions between oppositely charged polyelectrolytes (Overbeek and Voorn 1957; Srivastava and Tirrell 2016; Sing 2017; Lin et al. 2019). In the context of transcription, …

منتوجات جديدة

Pol II phosphorylation regulates a switch between …

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 …

منتوجات جديدة

Coactivator condensation at super-enhancers links …

Phase separation of coactivators compartmentalizes and concentrates the transcription apparatus. Enhancers are gene regulatory elements bound by transcription factors that recruit coactivators and the transcription apparatus (not shown) to regulate gene expression. Super-enhancers are clusters of enhancers bound by master transcription …

منتوجات جديدة

Coactivator condensation at super-enhancers links …

, and Richard A. Young. +18 authors. Authors Info & Affiliations. Science. 21 Jun 2018. Vol 361, Issue 6400. DOI: 10.1126/science.aar3958. …

منتوجات جديدة

Volume 18 Issue 12, December 2022

Clustering and multimerization of cell surface proteins (CSPs) are essential for triggering downstream intracellular signaling events. Membrane-anchored liquid–liquid phase-separation systems ...

منتوجات جديدة

Reentrant Liquid Condensate Phase of Proteins is Stabilized …

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. …

منتوجات جديدة

RNA-Mediated Feedback Control of Transcriptional Condensates

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 …

منتوجات جديدة

The RNA face of phase separation | Science

Phase separation or liquid unmixing—a phenomenon resembling the formation of oil droplets in vinegar—has emerged as a major driver of functional compartmentalization within cells, allowing the rapid and dynamic isolation of specific activities from the surrounding cellular environment, without the need of a membrane …