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 Mediator is ...

Richard YoungCellTranscription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains,Mediator（BioArt：Cell …

If the enrichment of signaling factors at super-enhancers occurs through the phase separation properties of their IDRs and incorporation into Mediator condensates, then mutations in the IDRs that affect their ability to form phase-separated droplets in vitro would be expected to affect their ability to target and activate genes in vivo.

In a phenomenon called complex coacervation, a type of liquid-liquid phase separation mediated by electrostatic interactions between oppositely charged polyelectrolytes, low levels of RNA can enhance condensate formation, whereas high levels can cause their dissolution (Lin et al., 2019; Overbeek and Voorn, 1957; Sing, 2017; Srivastava and ...

Young Tae Chang19, Anthony A. Hyman11,20, Nathanael S. Gray4,5, Richard A.Young1,3† The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates

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.

Richard Young. Professor of ... RA Young. Cell 130 (1), 77-88, 2007. 2317: 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. 2268: 2010: Coactivator condensation at super-enhancers links phase separation and ...

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 ...

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 complex1–4. The large subunit of Pol ;II ...

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 …

We propose that a phase separation model explains features of transcriptional control, including the formation of super-enhancers, the sensitivity of super-enhancers to perturbation, and their …

(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. …

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

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 ...

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 ...

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 …

Phase separation is an important mechanism for biomolecule condensate assembly and is involved in multiple biological activities. Understanding its molecular mechanism provides a unique ...

In a phenomenon called complex coacervation, a type of liquid-liquid phase separation mediated by electrostatic interactions between oppositely charged polyelectrolytes, low levels of RNA can enhance condensate formation, whereas high levels can cause their dissolution (Lin et al., 2019; Overbeek and Voorn, 1957; Sing, 2017; Srivastava and ...

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.

We show that the embryonic stem cell (ESC) pluripotency TF OCT4, the estrogen receptor (ER), and the yeast TF GCN4 form phase-separated condensates with Mediator and require the same amino acids or ligands for …

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.

Liquid–liquid phase separation emerges as a biophysical mechanism to form dynamic, multivalent condensates of TFs, mediators, ... Jaenisch R, Young R. Stem cells, the molecular circuitry of ...

Robert G. Roeder, Phillip A. Sharp, Arup K. Chakraborty, Richard A. Young† ... phase separation of coactivators, which is driven in part by high-valency and low-affinity interactions of intrinsically disordered regions. ON OUR WEBSITE ...

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:

2018621Richard Young ScienceCoactivator condensation at super-enhancers links phase separation and gene control【9】,BRD4MED1,, ...

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 .

Phase separation, in which macromolecules partition into a concentrated phase that is immiscible with a dilute phase, is involved with fundamental cellular processes across the tree of life. We ...

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.

Phase separation is a physicochemical process that leads to macromolecules, such as proteins and nucleic acids, compartmentalizing into condensed and dissolved phases [4](Fig. 1 A).This process is an important mechanism for functional partitioning in cells through specific aggregation of biological macromolecules [5, 6].Phase separation creates the initial conditions …

Regulation of biological processes typically incorporates mechanisms that initiate and terminate the process and, where understood, these mechanisms often involve feedback control. Regulation of transcription is a fundamental cellular process where the mechanisms involved in initiation have been stu …