المؤلفون: Rajendiran, Vignesh, Devaraju, Nivedhitha, Haddad, Mahdi, Ravi, Nithin Sam, Panigrahi, Lokesh, Paul, Joshua, Gopalakrishnan, Chandrasekar, Wyman, Stacia, Ariudainambi, Keerthiga, Mahalingam, Gokulnath, Periyasami, Yogapriya, Prasad, Kirti, George, Anila, Sukumaran, Dhiyaneshwaran, Gopinathan, Sandhiya, Pai, Aswin Anand, Nakamura, Yukio, Balasubramanian, Poonkuzhali, Ramalingam, Rajasekaran, Thangavel, Saravanabhavan, Velayudhan, Shaji R., Corn, Jacob E., Mackay, Joel P., Marepally, Srujan, Srivastava, Alok, Crossley, Merlin, Mohankumar, Kumarasamypet M.

المساهمون: Wellcome Trust DBT India Alliance, Australian Medical Council, India Ministry of Science & Technology Department of Biotechnology, Indian Council of Medical Research, Science and Engineering Research Board

المصدر: Molecular Therapy ; volume 32, issue 3, page 663-677 ; ISSN 1525-0016

مصطلحات موضوعية: Drug Discovery, Pharmacology, Genetics, Molecular Biology, Molecular Medicine

الإتاحة: https://doi.org/10.1016/j.ymthe.2024.01.023Test
https://api.elsevier.com/content/article/PII:S1525001624000236?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1525001624000236?httpAccept=text/plainTest

المؤلفون: Shieh, Christine, Jones, Natasha, Vanle, Brigitte, Au, Margaret, Huang, Alden Y, Silva, Ana PG, Lee, Hane, Douine, Emilie D, Otero, Maria G, Choi, Andrew, Grand, Katheryn, Taff, Ingrid P, Delgado, Mauricio R, Hajianpour, MJ, Seeley, Andrea, Rohena, Luis, Vernon, Hilary, Gripp, Karen W, Vergano, Samantha A, Mahida, Sonal, Naidu, Sakkubai, Sousa, Ana Berta, Wain, Karen E, Challman, Thomas D, Beek, Geoffrey, Basel, Donald, Ranells, Judith, Smith, Rosemarie, Yusupov, Roman, Freckmann, Mary-Louise, Ohden, Lisa, Davis-Keppen, Laura, Chitayat, David, Dowling, James J, Finkel, Richard, Dauber, Andrew, Spillmann, Rebecca, Pena, Loren DM, Metcalfe, Kay, Splitt, Miranda, Lachlan, Katherine, McKee, Shane A, Hurst, Jane, Fitzpatrick, David R, Morton, Jenny EV, Cox, Helen, Venkateswaran, Sunita, Young, Juan I, Marsh, Eric D, Nelson, Stanley F, Martinez, Julian A, Graham, John M, Kini, Usha, Mackay, Joel P, Pierson, Tyler Mark

المصدر: Genetics in Medicine. 22(5)

مصطلحات موضوعية: Genetics, Clinical Research, Congenital Structural Anomalies, Brain Disorders, Pediatric, Intellectual and Developmental Disabilities (IDD), 2.1 Biological and endogenous factors, Aetiology, Child, Female, GATA Transcription Factors, Humans, Intellectual Disability, Megalencephaly, Neurodevelopmental Disorders, Nucleosomes, Phenotype, Pregnancy, Repressor Proteins, GATAD2B, NuRD complex, apraxia of speech, chromatin remodeling, macrocephaly, Undiagnosed Diseases Network, GATAD2B, NuRD complex, apraxia of speech, chromatin remodeling, macrocephaly, Clinical Sciences, Genetics & Heredity

الوصف: PurposeDetermination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND).MethodsFifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex.ResultsSubjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners.ConclusionsA consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7683d0mfTest

المؤلفون: Shieh, Christine, Jones, Natasha, Vanle, Brigitte, Au, Margaret, Huang, Alden, Silva, Ana, Lee, Hane, Douine, Emilie, Otero, Maria, Choi, Andrew, Grand, Katheryn, Taff, Ingrid, Delgado, Mauricio, Hajianpour, M, Seeley, Andrea, Rohena, Luis, Vernon, Hilary, Gripp, Karen, Vergano, Samantha, Mahida, Sonal, Naidu, Sakkubai, Sousa, Ana, Wain, Karen, Challman, Thomas, Beek, Geoffrey, Basel, Donald, Ranells, Judith, Smith, Rosemarie, Yusupov, Roman, Freckmann, Mary-Louise, Ohden, Lisa, Davis-Keppen, Laura, Chitayat, David, Dowling, James, Finkel, Richard, Dauber, Andrew, Spillmann, Rebecca, Pena, Loren, Metcalfe, Kay, Splitt, Miranda, Lachlan, Katherine, McKee, Shane, Hurst, Jane, Fitzpatrick, David, Morton, Jenny, Cox, Helen, Venkateswaran, Sunita, Young, Juan, Marsh, Eric, Nelson, Stanley, Martinez, Julian, Graham, John, Kini, Usha, Mackay, Joel, Pierson, Tyler

المصدر: Genetics in Medicine. 22(4)

الوصف: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/53c7t7b0Test
https://escholarship.org/content/qt53c7t7b0/qt53c7t7b0.pdfTest

المؤلفون: De Franco, Simona, Vandenameele, Julie, Brans, Alain, Verlaine, Olivier, Bendak, Katerina, Damblon, Christian, Matagne, André, Segal, David J, Galleni, Moreno, Mackay, Joel P, Vandevenne, Marylène

المصدر: Scientific reports. 9(1)

الوصف: Transcriptomes consist of several classes of RNA that have wide-ranging but often poorly described functions and the deregulation of which leads to numerous diseases. Engineering of functionalized RNA-binding proteins (RBPs) could therefore have many applications. Our previous studies suggested that the RanBP2-type Zinc Finger (ZF) domain is a suitable scaffold to investigate the design of single-stranded RBPs. In the present work, we have analyzed the natural sequence specificity of various members of the RanBP2-type ZF family and characterized the interaction with their target RNA. Surprisingly, our data showed that natural RanBP2-type ZFs with different RNA-binding residues exhibit a similar sequence specificity and therefore no simple recognition code can be established. Despite this finding, different discriminative abilities were observed within the family. In addition, in order to target a long RNA sequence and therefore gain in specificity, we generated a 6-ZF array by combining ZFs from the RanBP2-type family but also from different families, in an effort to achieve a wider target sequence repertoire. We showed that this chimeric protein recognizes its target sequence (20 nucleotides), both in vitro and in living cells. Altogether, our results indicate that the use of ZFs in RBP design remains attractive even though engineering of specificity changes is challenging.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1t6189b9Test

المؤلفون: Herchenröther, Andreas, Gossen, Stefanie, Friedrich, Tobias, Reim, Alexander, Daus, Nadine, Diegmüller, Felix, Leers, Jörg, Sani, Hakimeh Moghaddas, Gerstner, Sarah, Schwarz, Leah, Stellmacher, Inga, Szymkowiak, Laura Victoria, Nist, Andrea, Stiewe, Thorsten, Borggrefe, Tilman, Mann, Matthias, Mackay, Joel P., Bartkuhn, Marek, Borchers, Annette, Lan, Jie, Hake, Sandra B.

مصطلحات موضوعية: ddc:570

الوصف: Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as a direct histone variant H2A.Z interactor involved in mitosis and craniofacial development. Here, we identify the H2A.Z/PWWP2A-associated protein HMG20A as part of several chromatin-modifying complexes, including NuRD, and show that it localizes to distinct genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis. Our data indicate that craniofacial malformations are caused by defects in neural crest cell (NCC) migration and cartilage formation. These developmental failures are phenocopied in Hmg20a-depleted mESCs, which show inefficient differentiation into NCCs and cardiomyocytes (CM). Consequently, loss of HMG20A, which marks open promoters and enhancers, results in chromatin accessibility changes and a striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and differentiation processes. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and reveal it as a key modulator of intricate developmental transcription programs that guide the differentiation of NCCs and CMs. ; Deutsche Forschungsgemeinschaft (DFG); ROR-ID:018mejw64

وصف الملف: application/pdf

العلاقة: https://jlupub.ub.uni-giessen.de//handle/jlupub/18521Test; http://dx.doi.org/10.22029/jlupub-17885Test

الإتاحة: https://doi.org/10.22029/jlupub-17885Test
https://jlupub.ub.uni-giessen.de//handle/jlupub/18521Test

المؤلفون: Jowsey, William J, Morris, Calum RP, Hall, Drew A, Sullivan, John T, Fagerlund, Robert D, Eto, Karina Y, Solomon, Paul D, Mackay, Joel P, Bond, Charles S, Ramsay, Josh, Ronson, Clive W

الوصف: Horizontal gene transfer is tightly regulated in bacteria. Often only a fraction of cells become donors even when regulation of horizontal transfer is coordinated at the cell population level by quorum sensing. Here, we reveal the widespread 'domain of unknown function' DUF2285 represents an 'extended-turn' variant of the helix-turn-helix domain that participates in both transcriptional activation and antiactivation to initiate or inhibit horizontal gene transfer. Transfer of the integrative and conjugative element ICEMlSymR7A is controlled by the DUF2285-containing transcriptional activator FseA. One side of the DUF2285 domain of FseA has a positively charged surface which is required for DNA binding, while the opposite side makes critical interdomain contacts with the N-terminal FseA DUF6499 domain. The QseM protein is an antiactivator of FseA and is composed of a DUF2285 domain with a negative surface charge. While QseM lacks the DUF6499 domain, it can bind the FseA DUF6499 domain and prevent transcriptional activation by FseA. DUF2285-domain proteins are encoded on mobile elements throughout the proteobacteria, suggesting regulation of gene transfer by DUF2285 domains is a widespread phenomenon. These findings provide a striking example of how antagonistic domain paralogues have evolved to provide robust molecular control over the initiation of horizontal gene transfer.

وصف الملف: fulltext

العلاقة: http://purl.org/au-research/grants/arc/FT170100235Test; http://hdl.handle.net/20.500.11937/92328Test

الإتاحة: https://doi.org/20.500.11937/92328Test
https://doi.org/10.1093/nar/gkad457Test
https://hdl.handle.net/20.500.11937/92328Test

المؤلفون: Loo, Lipin, Waller, Matthew A., Moreno, Cesar L., Cole, Alexander J., Stella, Alberto Ospina, Pop, Oltin-Tiberiu, Jochum, Ann-Kristin, Ali, Omar Hasan, Denes, Christopher E., Hamoudi, Zina, Chung, Felicity, Aggarwal, Anupriya, Low, Jason K. K., Patel, Karishma, Siddiquee, Rezwan, Kang, Taeyoung, Mathivanan, Suresh, Mackay, Joel P., Jochum, Wolfram, Flatz, Lukas, Hesselson, Daniel, Turville, Stuart, Neely, G. Gregory

المساهمون: Cadwell, Ken, National Health and Medical Research Council, University of Sydney, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

المصدر: PLOS Biology ; volume 21, issue 2, page e3001967 ; ISSN 1545-7885

الوصف: Although ACE2 is the primary receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here, we use whole-genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was a TLR -related cell surface receptor called leucine-rich repeat-containing protein 15 ( LRRC15 ). LRRC15 expression was sufficient to promote SARS-CoV-2 spike binding where they form a cell surface complex. LRRC15 mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe Coronavirus Disease 2019 (COVID-19) infection where it can be found lining the airways. Mechanistically, LRRC15 does not itself support SARS-CoV-2 infection, but fibroblasts expressing LRRC15 can suppress both pseudotyped and authentic SARS-CoV-2 infection in trans . Moreover, LRRC15 expression in fibroblasts suppresses collagen production and promotes expression of IFIT, OAS, and MX-family antiviral factors. Overall, LRRC15 is a novel SARS-CoV-2 spike-binding receptor that can help control viral load and regulate antiviral and antifibrotic transcriptional programs in the context of COVID-19 infection.

الإتاحة: https://doi.org/10.1371/journal.pbio.3001967Test

المؤلفون: Arvindekar, Shreyas M., Jackman, Matthew J., Low, Jason K.K., Landsberg, Michael J., Mackay, Joel P., Viswanath, Shruthi

المصدر: Biophysical Journal ; volume 122, issue 3, page 472a ; ISSN 0006-3495

مصطلحات موضوعية: Biophysics

الإتاحة: https://doi.org/10.1016/j.bpj.2022.11.2531Test
https://api.elsevier.com/content/article/PII:S0006349522034476?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0006349522034476?httpAccept=text/plainTest

المؤلفون: Low, Jason K.K., Patel, Karishma, Jones, Natasha, Solomon, Paul, Norman, Alexander, Maxwell, Joshua W.C., Pachl, Petr, Matthews, Jacqueline M., Payne, Richard J., Passioura, Toby, Suga, Hiroaki, Walport, Louise J., Mackay, Joel P.

المساهمون: Francis Crick Institute, Medical Research Council, Australian Nuclear Science and Technology Organisation, Cancer Research UK, National Health and Medical Research Council, National Institute of Health and Medical Research, Wellcome Trust

المصدر: Journal of Biological Chemistry ; volume 299, issue 12, page 105482 ; ISSN 0021-9258

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1016/j.jbc.2023.105482Test
https://api.elsevier.com/content/article/PII:S0021925823025103?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0021925823025103?httpAccept=text/plainTest

المؤلفون: Werren, Elizabeth A., Guxholli, Alba, Jones, Natasha, Wagner, Matias, Hannibal, Iris, Granadillo, Jorge L., Tyndall, Amanda V., Moccia, Amanda, Kuehl, Ryan, Levandoski, Kristin M., Day-Salvatore, Debra L., Wheeler, Marsha, Chong, Jessica X., Bamshad, Michael J., Innes, A. Micheil, Pierson, Tyler Mark, Mackay, Joel P., Bielas, Stephanie L., Martin, Donna M.

المصدر: Human Genetics and Genomics Advances ; volume 4, issue 3, page 100198 ; ISSN 2666-2477

مصطلحات موضوعية: Genetics (clinical), Molecular Medicine

الإتاحة: https://doi.org/10.1016/j.xhgg.2023.100198Test
https://api.elsevier.com/content/article/PII:S2666247723000301?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666247723000301?httpAccept=text/plainTest