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Meis1

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https://www.readbyqxmd.com/read/29317485/meis1-coordinates-cerebellar-granule-cell-development-by-regulating-pax6-transcription-bmp-signaling-and-atoh1-degradation
#1
Tomoo Owa, Shinichiro Taya, Satoshi Miyashita, Mariko Yamashita, Toma Adachi, Koyo Yamada, Miwa Yokoyama, Shogo Aida, Tomoki Nishioka, Yukiko U Inoue, Ryo Goitsuka, Takuro Nakamura, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino
Cerebellar granule cell precursors (GCPs) and granule cells (GCs) represent good models to study neuronal development. Here we report that the transcription factor, Meis1, plays pivotal roles to regulate mouse GC development. We found that Meis1 is expressed in granule cell lineage cells and astrocytes in the cerebellum during development. Targeted disruption of the Meis1 gene specifically in the GC lineage resulted in smaller cerebella with disorganized lobules. Knockdown/knockout experiments for Meis1 as well as in vitro assays show that Meis1 binds to an upstream sequence of Pax6 to enhance its transcription in GCPs/GCs and further suggested that the Meis1-Pax6 cascade regulates morphology of GCPs/GCs during development...
January 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29296870/a-knock-in-mouse-strain-facilitates-dynamic-tracking-and-enrichment-of-meis1
#2
Ping Xiang, Wei Wei, Nicole Hofs, Jack Clemans-Gibbon, Tobias Maetzig, Courteney K Lai, Ishpreet Dhillon, Christopher May, Jens Ruschmann, Edith Schneider, Patricia Rosten, Kaiji Hu, Florian Kuchenbauer, Pamela A Hoodless, R Keith Humphries
Myeloid ecotropic viral integration site 1 (MEIS1), a HOX transcription cofactor, is a critical regulator of normal hematopoiesis, and its overexpression is implicated in a wide range of leukemias. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) gene-editing system, we generated a knock-in transgenic mouse line in which a green fluorescent protein (GFP) reporter and a hemagglutinin (HA) epitope tag are inserted near the translational start site of endogenous Meis1...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29240787/brd3-4-inhibition-and-flt3-ligand-deprivation-target-pathways-that-are-essential-for-the-survival-of-human-mll-af9-leukemic-cells
#3
Marco Carretta, Annet Z Brouwers-Vos, Matthieu Bosman, Sarah J Horton, Joost H A Martens, Edo Vellenga, Jan Jacob Schuringa
In the present work we aimed to identify targetable signaling networks in human MLL-AF9 leukemias. We show that MLL-AF9 cells critically depend on FLT3-ligand induced pathways as well as on BRD3/4 for their survival. We evaluated the in vitro and in vivo efficacy of the BRD3/4 inhibitor I-BET151 in various human MLL-AF9 (primary) models and patient samples and analyzed the transcriptome changes following treatment. To further understand the mode of action of BRD3/4 inhibition, we performed ChIP-seq experiments on the MLL-AF9 complex in THP1 cells and compared it to RNA-seq data of I-BET151 treated cells...
2017: PloS One
https://www.readbyqxmd.com/read/29217774/microrna-155-is-a-direct-target-of-meis1-but-not-a-driver-in-acute-myeloid-leukemia
#4
Edith Schneider, Anna Staffas, Linda Röhner, Erik D Malmberg, Arghavan Ashouri, Kathrin Krowiorz, Nicole Pochert, Christina Miller, Stella Yuan Wei, Laleh Arabanian, Christian Buske, Hartmut Döhner, Lars Bullinger, Linda Fogelstrand, Michael Heuser, Konstanze Döhner, Ping Xiang, Jens Ruschmann, Oleh I Petriv, Alireza Heravi-Moussavi, Carl L Hansen, Martin Hirst, R Keith Humphries, Arefeh Rouhi, Lars Palmqvist, Florian Kuchenbauer
MicroRNA-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR 155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo. However, in the absence or after the removal of miR-155, leukemia onset and progression were unaffected...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29217648/the-interaction-of-enl-with-paf1-mitigates-polycomb-silencing-and-facilitates-murine-leukemogenesis
#5
Katrin Hetzner, Maria-Paz Garcia-Cuellar, Christian Büttner, Robert K Slany
ENL is a chromatin reader present in complexes stimulating transcriptional elongation. It is fused to MLL in leukemia and missense mutations have been identified in Wilms' tumor and AML. Here we demonstrate that ENL overcomes polycomb silencing through recruitment of PAF1 via the conserved YEATS domain that recognizes acetylated histone H3. PAF1 was responsible for anti-repressive activities of ENL in vitro and it determined the transforming potential of MLL-ENL. MLL-ENL target loci showed supraphysiological PAF1 binding, hyper-ubiquitination of histone H2B and hypomodification with H2AUb resulting in accelerated transcription rates...
December 7, 2017: Blood
https://www.readbyqxmd.com/read/29194616/comparative-analysis-of-single-cell-rna-sequencing-data-from-mouse-spermatogonial-and-mesenchymal-stem-cells-to-identify-differentially-expressed-genes-and-transcriptional-regulators-of-germline-cells
#6
Sajjad Sisakhtnezhad, Parvin Heshmati
Identifying effective internal factors for regulating germline commitment during development and for maintaining spermatogonial stem cells (SSCs) self-renewal is important to understand the molecular basis of spermatogenesis process, and to develop new protocols for the production of the germline cells from other cell sources. Therefore, this study was designed to investigate single-cell RNA-sequencing data for identification of differentially expressed genes (DEGs) in 12 mouse-derived single SSCs (mSSCs) in compare with 16 mouse-derived single mesenchymal stem cells...
December 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29183737/cross-platform-single-cell-analysis-of-kidney-development-shows-stromal-cells-express-gdnf
#7
Bliss Magella, Mike Adam, Andrew S Potter, Meenakshi Venkatasubramanian, Kashish Chetal, Stuart B Hay, Nathan Salomonis, S Steven Potter
The developing kidney provides a useful model for study of the principles of organogenesis. In this report we use three independent platforms, Drop-Seq, Chromium 10x Genomics and Fluidigm C1, to carry out single cell RNA-Seq (scRNA-Seq) analysis of the E14.5 mouse kidney. Using the software AltAnalyze, in conjunction with the unsupervised approach ICGS, we were unable to identify and confirm the presence of 16 distinct cell populations during this stage of active nephrogenesis. Using a novel integrative supervised computational strategy, we were able to successfully harmonize and compare the cell profiles across all three technological platforms...
November 25, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29163810/myeloid-ecotropic-viral-integration-site-1-inhibits-cell-proliferation-invasion-or-migration-in-human-gastric-cancer
#8
Fei Song, Hong Wang, Yingying Wang
Myeloid ecotropic viral integration site 1 (MEIS1) has been identified to be a potential tumor suppressor in some cancers. However, the mechanisms underlying MEIS1-induced cancer development and progression were not clear. Here, we investigated the expression and role of MEIS1 in gastric cancer. In vivo, we analyzed tumor growth using nude mice model. In the present study, MEIS1 expression was obviously decreased in GC cell lines compared with that in normal gastric cell lines (all p<0.001). MEIS1 overexpression inhibited cell proliferation and G1/S transition accompanied by decreased Cyclin D1 and Cyclin A expression...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29033051/genetics-of-restless-legs-syndrome-an-update
#9
REVIEW
Félix J Jiménez-Jiménez, Hortensia Alonso-Navarro, Elena García-Martín, José A G Agúndez
A major role of genetic factors in the risk of developing restless legs syndrome (RLS) is supported by the high frequency of positive family history of RLS in patients affected with this disease, and the higher concordance rates in monozygotic twins compared with dizygotic ones in twin studies. In this review we have focused on those reports describing inheritance patterns of RLS, genetic anticipation, the results of studies performed on positivity of family history of RLS, twin studies, linkage studies in familial RLS, genome-wide association studies (GWAS), exome sequencing studies, and case-control association studies on candidate genes in RLS...
August 31, 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/29029846/identification-of-novel-risk-loci-for-restless-legs-syndrome-in-genome-wide-association-studies-in-individuals-of-european-ancestry-a-meta-analysis
#10
REVIEW
Barbara Schormair, Chen Zhao, Steven Bell, Erik Tilch, Aaro V Salminen, Benno Pütz, Yves Dauvilliers, Ambra Stefani, Birgit Högl, Werner Poewe, David Kemlink, Karel Sonka, Cornelius G Bachmann, Walter Paulus, Claudia Trenkwalder, Wolfgang H Oertel, Magdolna Hornyak, Maris Teder-Laving, Andres Metspalu, Georgios M Hadjigeorgiou, Olli Polo, Ingo Fietze, Owen A Ross, Zbigniew Wszolek, Adam S Butterworth, Nicole Soranzo, Willem H Ouwehand, David J Roberts, John Danesh, Richard P Allen, Christopher J Earley, William G Ondo, Lan Xiong, Jacques Montplaisir, Ziv Gan-Or, Markus Perola, Pavel Vodicka, Christian Dina, Andre Franke, Lukas Tittmann, Alexandre F R Stewart, Svati H Shah, Christian Gieger, Annette Peters, Guy A Rouleau, Klaus Berger, Konrad Oexle, Emanuele Di Angelantonio, David A Hinds, Bertram Müller-Myhsok, Juliane Winkelmann
BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry...
November 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29019697/development-of-potent-type-i-protein-arginine-methyltransferase-prmt-inhibitors-of-leukemia-cell-proliferation
#11
Chen Wang, Hao Jiang, Jia Jin, Yiqian Xie, Zhifeng Chen, Hao Zhang, Fulin Lian, Yu-Chih Liu, Chenhua Zhang, Hong Ding, Shijie Chen, Naixia Zhang, Yuanyuan Zhang, Hualiang Jiang, Kaixian Chen, Fei Ye, Zhiyi Yao, Cheng Luo
Protein Arginine Methyltransferases (PRMTs) are crucial players in diverse biological processes, and dysregulation of PRMTs has been linked to various human diseases, especially cancer. Therefore, small molecules targeting PRMTs have profound impact for both academic functional studies and clinical disease treatment. Here, we report the discovery of N(1)-(2-((2-chlorophenyl)thio)benzyl)-N(1)-methylethane-1,2-diamine (28d, DCPR049_12), a highly potent inhibitor of type I PRMTs that has good selectivity against a panel of other methyltransferases...
October 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28960191/meis2-as-a-critical-player-in-mn1-induced-leukemia
#12
C K Lai, G L Norddahl, T Maetzig, P Rosten, T Lohr, L Sanchez Milde, N von Krosigk, T R Docking, M Heuser, A Karsan, R K Humphries
Meningioma 1 (MN1) is an independent prognostic marker for normal karyotype acute myeloid leukemia (AML), with high expression linked to all-trans retinoic acid resistance and poor survival. MN1 is also a potent and sufficient oncogene in murine leukemia models, strongly dependent on the MEIS1/AbdB-like HOX protein complex to transform common myeloid progenitors, block myeloid differentiation, and promote leukemic stem cell self-renewal. To identify key genes and pathways underlying leukemic activity, we functionally assessed MN1 cell phenotypic heterogeneity, revealing leukemic and non-leukemic subsets...
September 29, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28956216/creb-nf-y-and-meis1-conserved-binding-sites-are-essential-to-balance-myostatin-promoter-enhancer-activity-during-early-myogenesis
#13
Carla Vermeulen Carvalho Grade, Carolina Stefano Mantovani, Marina Alves Fontoura, Faisal Yusuf, Beate Brand-Saberi, Lúcia Elvira Alvares
Myostatin (MSTN) is a strong inhibitor of skeletal muscle growth in human and other vertebrates. Its transcription is controlled by a proximal promoter/enhancer (Mstn P/E) containing a TATA box besides CREB, NF-Y, MEIS1 and FXR transcription factor binding sites (TFBSs), which are conserved throughout evolution. The aim of this work was to investigate the role of these TFBSs on Mstn P/E activity and evaluate the potential of their putative ligands as Mstn trans regulators. Mstn P/E mutant constructs were used to establish the role of conserved TFBSs using dual-luciferase assays...
October 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28841467/chronological-age-prediction-based-on-dna-methylation-massive-parallel-sequencing-and-random-forest-regression
#14
Jana Naue, Huub C J Hoefsloot, Olaf R F Mook, Laura Rijlaarsdam-Hoekstra, Marloes C H van der Zwalm, Peter Henneman, Ate D Kloosterman, Pernette J Verschure
The use of DNA methylation (DNAm) to obtain additional information in forensic investigations showed to be a promising and increasing field of interest. Prediction of the chronological age based on age-dependent changes in the DNAm of specific CpG sites within the genome is one such potential application. Here we present an age-prediction tool for whole blood based on massive parallel sequencing (MPS) and a random forest machine learning algorithm. MPS allows accurate DNAm determination of pre-selected markers and neighboring CpG-sites to identify the best age-predictive markers for the age-prediction tool...
August 1, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28830460/gene-mutational-pattern-and-expression-level-in-560-acute-myeloid-leukemia-patients-and-their-clinical-relevance
#15
Yong-Mei Zhu, Pan-Pan Wang, Jin-Yan Huang, Yun-Shuo Chen, Bing Chen, Yu-Jun Dai, Han Yan, Yi Hu, Wen-Yan Cheng, Ting-Ting Ma, Sai-Juan Chen, Yang Shen
BACKGROUND: Cytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML. METHODS: In this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1...
August 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28782694/co-regulation-of-micrornas-and-transcription-factors-in-cardiomyocyte-specific-differentiation-of-murine-embryonic-stem-cells-an-aspect-from-transcriptome-analysis
#16
Lin Gan, Bernd Denecke
The differentiation process of embryonic stem cells is a comprehensive process regulated by a variety of factors in response to stimulus. Studies of this process can be focused on cell biology as well as on molecular biology level. In this paper we identified the co-regulation of molecular regulators and their interactions during cardiomyocyte specific differentiation of mouse embryonic stem cells based on parallel genome wide transcriptome analyses of mRNA and microRNA. Differentially expressed mRNAs and microRNAs were identified according to their expression profiles...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28751478/novel-gene-and-network-associations-found-for-acute-lymphoblastic-leukemia-using-case-control-and-family-based-studies-in-multiethnic-populations
#17
Priyanka Nakka, Natalie P Archer, Heng Xu, Philip J Lupo, Benjamin J Raphael, Jun J Yang, Sohini Ramachandran
Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, suggesting that germline variants influence ALL risk. Although multiple genome-wide association (GWA) studies have identified variants predisposing children to ALL, it remains unclear whether genetic heterogeneity affects ALL susceptibility and how interactions within and among genes containing ALL-associated variants influence ALL risk.Methods: Here, we jointly analyzed two published datasets of case-control GWA summary statistics along with germline data from ALL case-parent trios...
October 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28745213/emerging-roles-of-meis1-in-cardiac-regeneration-stem-cells-and-cancer
#18
Merve Aksoz, Raife Dilek Turan, Esra Albayrak, Fatih Kocabas
Meis1 is a member of three-amino-acid loop extension (TALE) homeodomain transcription factors. Studies in the last decade have shown that Meis1 has crucial roles in cardiac regeneration, stem cell function, and tumorigenesis. We have recently demonstrated that knocking out of Meis1 in adult cardiomyocytes resulted in the induction of cardiomyocyte proliferation. This suggests that targeting of Meis1 might be utilized in the manipulation of cardiomyocyte cell cycle post cardiac injuries. In addition, hematopoietic stem cell (HSC) specific deletion of Meis1 leads to in vivo expansion of HSCs pool...
July 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28735443/retinoic-acid-regulates-avian-lung-branching-through-a-molecular-network
#19
Hugo Fernandes-Silva, Patrícia Vaz-Cunha, Violina Baranauskaite Barbosa, Carla Silva-Gonçalves, Jorge Correia-Pinto, Rute Silva Moura
Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development...
December 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28707666/-identification-of-proteins-associated-with-transcription-factors-hoxa9-and-e2a-pbx1-by-tandem-affinity-purification
#20
E A Shestakova, M Boutin, S Bourassa, E Bonneil, J J Bijl
Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations...
May 2017: Molekuliarnaia Biologiia
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