Partitioning of cancer therapeutics in nuclear condensates
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. ... Richard A Young 21 ... 21 Whitehead …
اقرأ أكثر
RNA in formation and regulation of transcriptional …
and Richard A. Young5 AFFILIATIONS: 1Koch Institute for Integrative Cancer Research, ... transcription factors, condensate, phase separation, intrinsically disordered domains . Phillip A. Sharp 2 ABSTRACT: Macrosopic membraneless organelles containing RNA such as the nucleoli, germ granules and the Cajal body have been known for decades. These ...
اقرأ أكثر
Transcription factors activate genes through the phase separation
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 .
اقرأ أكثر
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 that is phosphorylated by cyclin-dependent kinases during the transition from initiation to elongation, thus influencing the interaction of the …
اقرأ أكثر
Learning the chemical grammar of biomolecular condensates
Weak multivalent interactions are thought to drive formation of condensates through phase separation 16,17,18,20 ... Henry R. Kilgore & Richard A. Young. Department of Biology, Massachusetts ...
اقرأ أكثر
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
اقرأ أكثر
A Phase Separation Model for Transcriptional Control
(B) Chromatin immunoprecipitation sequencing (ChIP-seq) binding profiles for RNA polymerase II (RNA Pol II) and the indicated transcriptional cofactors and chromatin regulators at the POLE4 and miR-290-295 loci in murine embryonic stem cells. The transcription factor binding profile is a merged ChIP-seq binding profile of the TFs Oct4, Sox2, and Nanog. …
اقرأ أكثر
Chinese Medical Journal
Introduction. Phase separation (PS) is a phenomenon in which a mixture of molecules spontaneously separates into two distinct phases [], with varying compositions and concentrations of specific factors.In cells, liquid–liquid phase separation (LLPS) resembles the demixing of oil and water as it forms dense, droplet-like structures within a dilute surrounding …
اقرأ أكثر
A phase separation model predicts key features of …
Models and features of super-enhancers and typical enhancers. A. Schematic depiction of the classic model of co-operativity exemplified for typical enhancers and super-enhancers. The higher density of transcriptional regulators (referred to as "activators") through co-operative binding to DNA binding sites is thought to contribute to both higher transcriptional …
اقرأ أكثر
A Phase Separation Model for Transcriptional Control
Phase-separated multi-molecular assemblies provide a general regulatory mechanism to compartmentalize biochemical reactions within cells. We propose that a phase …
اقرأ أكثر
Science
2018621Richard Young ScienceCoactivator condensation at super-enhancers links phase separation and gene control【9】,BRD4MED1 …
اقرأ أكثر
Properties governing small-molecule partitioning into …
Phase separation Properties governing small-molecule ... Kilgore, Young and coworkers independently investigated the ... Swarnendu Tripathi 1 & Richard Kriwacki 1,2 1Department of Structural ...
اقرأ أكثر
Activating a new understanding of gene regulation
Research from the lab of Whitehead Member Richard Young and others earlier this year reported that such compartmentalization is a crucial, previously unobserved aspect of gene regulation.[1] ... within the environment of the cell — like oil refusing to mix with vinegar in a salad dressing — is called phase separation.
اقرأ أكثر
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. Here we show …
اقرأ أكثر
Coactivator condensation at super-enhancers links phase …
A proposed function of phase separation at SEs is the ability to compartmentalize and concentrate factors within a biomolecular condensate, so we sought to test whether MED1-IDR droplets could recapitulate this compartmentalization function in vitro.
اقرأ أكثر
Group Schuijers
During his postdoc in the lab of Prof. Dr. Richard Young (Whitehead institute/MIT) he continued studying signaling-driven transcription and uncovered how super-enhancers, clusters of enhancers that accumulate a disproportionate amount of transcriptional co-factors, serve as signal integration platforms for key cell identity genes ...
اقرأ أكثر
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 …
اقرأ أكثر
Transcription Factors Activate Genes through the Phase-Separation …
Phase separation provides a mechanism by which such gene products result in aberrant gene expression programs; by recruiting a disordered protein to the chromatin, diverse coactivators may form phase-separated condensates to drive oncogene expression. ... Richard A. Young ([email protected]). Experimental Model and Subject Details Cells. V6.5 ...
اقرأ أكثر
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.
اقرأ أكثر
Phase separation in biology
A synthetic phase separation system consisting of two protein components with tunable parameters was developed to visualize and characterize phase diagrams in living cells, revealing that ...
اقرأ أكثر
Learning the chemical grammar of biomolecular condensates
A study exploring the roles of diverse amino acids in promoting phase separation and influencing the material properties of condensates formed by a class of proteins.
اقرأ أكثر
bioRxiv |, …
, HymanRichard YoungDewpoint Therapeutics,ALS。 ... Molliex, A., et al.,Phase separation by low complexitydomains promotes stress granule assembly and drives pathologicalfibrillization.Cell, 2015. 163(1):p ...
اقرأ أكثر
Transcription factors interact with RNA to regulate genes
Correspondence and material requests should be addressed to Richard A. Young, [email protected]. ... The linear gradient was 3 minutes until switching the valve at 2% mobile phase B and increasing to 25% by 90 minutes and 45% by 120 minutes at a flow rate of 300 nL/minute. Peptides were separated on a laser-pulled 75 μm ID and 30 cm length ...
اقرأ أكثر
Biomolecular Condensates and Cancer
Condensates are membrane-less bodies, often formed by liquid-liquid phase separation, that compartmentalize protein and RNA molecules with related functions. New insights from condensate studies portend a profound transformation in our understanding of cellular dysregulation in cancer.
اقرأ أكثر
Dr. Richard A. Young, MD | San Mateo, CA
Dr. Richard A. Young has expertise in treating chronic diabetes, ... Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains. Ann Boija, Isaac A ...
اقرأ أكثر
Phase Separation in Biology and Disease; Current …
A truncation of an IDR can abrogate phase separation, and may lead to a phenotype. However, we argue that this experiment is not sufficient to conclude that phase separation is important for the biological function. This is because there is a second, competing hypothesis that the IDR was crucial for biological function through a mechanism(s ...
اقرأ أكثر
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 a new …
اقرأ أكثر
Richard Young
Richard Young. Professor of ... RA Young. Cell 130 (1), 77-88, 2007. 2303: 2007: Mediator and cohesin connect gene expression and chromatin architecture. MH Kagey, JJ Newman, S Bilodeau, Y Zhan, DA Orlando, NL van Berkum, ... Nature 467 (7314), 430-435, 2010. 2253: 2010: Coactivator condensation at super-enhancers links phase separation and ...
اقرأ أكثر