In Candida albicans the transcription factor Efg1, which is differentially expressed in the white phase of the white-opaque transition, is essential for expression of the white phenotype. It is one of six transcription factors included in a proposed interactive transcription network regulating white-opaque switching and maintenance of the alternative phenotypes. Ten sites were identified in the EFG1 promoter that differentially bind one or more of the network transcription factors in the white and/or opaque phase. To explore the functionality of these binding sites in the differential expression of EFG1, we generated targeted deletions of each of the 10 binding sites, combinatorial deletions, and regional deletions using a Renilla reniformis luciferase reporter system. Individually targeted deletion of only four of the 10 sites had minor effects consistent with differential expression of EFG1, and only in the opaque phase. Alternative explanations are considered.
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http://dx.doi.org/10.1534/g3.116.029785 | DOI Listing |
Clin Epigenetics
December 2024
Hereditary Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.
View Article and Find Full Text PDFCurr Opin Struct Biol
December 2024
Univ. Grenoble Alpes, CEA, CNRS, IBS, Grenoble, France. Electronic address:
Advances in the characterization of intrinsically disordered proteins (IDPs) have unveiled a remarkably complex and diverse interaction landscape, including coupled folding and binding, highly dynamic complexes, multivalent interactions, and even interactions between entirely disordered proteins. Here we review recent examples of IDP binding mechanisms elucidated by experimental techniques such as nuclear magnetic resonance spectroscopy, single-molecule Förster resonance energy transfer, and stopped-flow fluorescence. These techniques provide insights into the structural details of transition pathways and complex intermediates, and they capture the dynamics of IDPs within complexes.
View Article and Find Full Text PDFBioorg Chem
December 2024
Laboratory of Molecular Chemistry, Materials and Environment (LCM2E), Department of Chemistry, Multidisciplinary Faculty of Nador, University Mohamed I, 60700 Nador, Morocco. Electronic address:
Given the ease of synthetic accessibility and the promising biological profile demonstrated by both imidazo[1,2-a]pyridine and Chalcone derivatives, a series of Chalcone-based imidazo[1,2-a]pyridine derivatives were synthesized and characterized using H NMR, C NMR, Mass Spectrometry and FTIR techniques. Density functional theory (DFT) was employed to investigate the structural and electronic properties, providing insights into potential reactive sites. The synthesized compounds were evaluated in vitro for their antiviral properties against human immunodeficiency virus type-1 (HIV-1) and human immunodeficiency virus type-2 (HIV-2) in MT-4 cells.
View Article and Find Full Text PDFAdv Mater
December 2024
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids and State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Highly efficient nonfullerene acceptors (NFAs) for organic solar cells (OSCs) with low energy loss (E) and favorable morphology are critical for breaking the efficiency bottleneck and achieving commercial applications of OSCs. In this work, quinoxaline-based NFAs are designed and synthesized using a synergistic isomerization and bromination approach. The π-expanded quinoxaline-fused core exhibits different bromination sites for isomeric NFAs, namely AQx-21 and AQx-22.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
Cone cGMP-phosphodiesterase (PDE6) is the key effector enzyme for daylight vision, and its properties are critical for shaping distinct physiology of cone photoreceptors. We determined the structures of human cone PDE6C in various liganded states by single-particle cryo-EM that reveal essential functional dynamics and adaptations of the enzyme. Our analysis exposed the dynamic nature of PDE6C association with its regulatory γ-subunit (Pγ) which allows openings of the catalytic pocket in the absence of phototransduction signaling, thereby controlling photoreceptor noise and sensitivity.
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