Organization and regulation of gene transcription

Nature, Journal Year: 2019, Volume and Issue: 573(7772), P. 45 - 54

Published: Aug. 28, 2019

Language: Английский

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Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases

Science China Life Sciences, Journal Year: 2020, Volume and Issue: 63(7), P. 953 - 985

Published: April 30, 2020

Language: Английский

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A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers

Cell, Journal Year: 2019, Volume and Issue: 178(5), P. 1145 - 1158.e20

Published: Aug. 1, 2019

Language: Английский

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Transcriptional Regulation of Wnt/β-Catenin Pathway in Colorectal Cancer

Cells, Journal Year: 2020, Volume and Issue: 9(9), P. 2125 - 2125

Published: Sept. 19, 2020

The Wnt/β-catenin signaling pathway exerts integral roles in embryogenesis and adult homeostasis. Aberrant activation of the is implicated growth-associated diseases cancers, especially as a key driver initiation progression colorectal cancer (CRC). Loss or inactivation Adenomatous polyposis coli (APC) results constitutive signaling, which considered an initiating event development CRC. Increased observed virtually all CRC patients, underscoring importance this for therapeutic intervention. Prior studies have deciphered regulatory networks required cytoplasmic stabilisation degradation Wnt effector, β-catenin. However, mechanism whereby nuclear β-catenin drives inhibits expression target genes more diverse less well characterised. Here, we describe brief synopsis core canonical components, set spotlight on mediators highlight emerging role chromatin regulators modulators β-catenin-dependent transcription activity oncogenic output.

Language: Английский

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Structure of the human Mediator-bound transcription preinitiation complex

Science, Journal Year: 2021, Volume and Issue: 372(6537), P. 52 - 56

Published: March 11, 2021

Mediating transcription The Mediator complex is recruited by factors to all protein-coding genes in eukaryotes and helps assemble the machinery necessary transcribe gene. Abdella et al. present cryo–electron microscopy structure of human Mediator-bound preinitiation (Med-PIC). shows how positions long, flexible C-terminal domain RNA polymerase II be phosphorylated kinase CDK7, a crucial step for further processing into mature RNA. Most sites where bind are flexibly tethered complex, allowing large Med-PIC at any Science , this issue p. 52

Language: Английский

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Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8969 - 8969

Published: Aug. 20, 2021

In mammalian cells, two cellular organelles, mitochondria and peroxisomes, share the ability to degrade fatty acid chains. Although each organelle harbors its own β-oxidation pathway, a distinct mitochondrial system feeds oxidative phosphorylation pathway for ATP synthesis. At same time, peroxisomal participates in thermogenesis. A scientific milestone 1965 helped discover hepatomegaly effect rat liver by clofibrate, subsequently identified as peroxisome proliferator rodents an activator of pathway. These proliferators were later activating ligands Peroxisome Proliferator-Activated Receptor α (PPARα), cloned 1990. The ligand-activated heterodimer PPARα/RXRα recognizes DNA sequence, called PPRE (Peroxisome Proliferator Response Element), corresponding half-consensus hexanucleotide motifs, AGGTCA, separated one nucleotide. Accordingly, assembled complex containing PPRE/PPARα/RXRα/ligands/Coregulators controls expression genes involved β-oxidation. This review mobilizes considerable number findings that discuss miscellaneous axes, covering detailed pattern PPARα species tissues, lessons from several KO mouse models modulation function dietary micronutrients.

Language: Английский

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Structures of the human Mediator and Mediator-bound preinitiation complex

Science, Journal Year: 2021, Volume and Issue: 372(6546)

Published: May 7, 2021

A complete PIC-Mediator structure As a critical transcription coactivator, the multisubunit Mediator complex binds RNA polymerase II (Pol II), facilitates preinitiation (PIC) assembly, and stimulates phosphorylation of Pol C-terminal domain (CTD). However, how these transcriptional events are coordinated by is not fully understood. Chen et al. determined structures human Mediator-bound PIC in distinct conformational states, latter which represents assembled on 14-subunit factor IID (TFIID). The show that undergoes reorganization during sandwiches CTD, works with TFIID to organize TFIIH for initiation. Science , abg0635, this issue p. eabg0635

Language: Английский

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Second generation androgen receptor antagonists and challenges in prostate cancer treatment

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(7)

Published: July 21, 2022

Abstract Prostate cancer is a hormone-dependent malignancy, whose onset and progression are closely related to the activity of androgen receptor (AR) signaling pathway. Due this critical role AR in driving prostate cancer, therapy targeting pathway has been mainstay strategy for metastatic treatment. The utility these agents expanded with emergence second-generation antagonists, which began approval enzalutamide 2012 by United States Food Drug Administration (FDA). Together apalutamide darolutamide, were approved 2018 2019, respectively, have improved survival patients applications both androgen-dependent castration-resistant disease. While receiving drugs receive benefit form prolonged survival, they not cured ultimately progress lethal neuroendocrine (NEPC). Here we summarize current state antagonist development highlight emerging challenges their clinical application potential resistance mechanisms, might be addressed combination therapies or novel AR-targeted therapies.

Language: Английский

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CycC1;1–WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis

The Plant Cell, Journal Year: 2023, Volume and Issue: 35(7), P. 2570 - 2591

Published: April 11, 2023

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription dynamically regulated in response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates tolerance by interfering with WRKY75-mediated transcriptional activation Arabidopsis (Arabidopsis thaliana). Disruption CycC1;1 promotes expression and because interferes RNA polymerase II recruitment occupying the promoter. Enhanced cycc1;1 mutant was completely compromised an mutation. Moreover, physically interacts factor WRKY75, which can bind promoter activate expression. In contrast mutant, wrky75 has attenuated tolerance, whereas overexpression rescues sensitivity wrky75. Intriguingly, inhibits via their interaction. Thus, increased were abolished WRKY75 Our findings demonstrate forms complex inactivate under low conditions. By contrast, high conditions, are activated at least partially but decreased

Language: Английский

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Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(4), P. 574 - 589.e8

Published: Aug. 17, 2020

Language: Английский

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