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https://www.readbyqxmd.com/read/27920635/clinical-and-molecular-characterisation-of-children-with-pierre-robin-sequence-and-additional-anomalies
#1
Jessie X Xu, Nicky Kilpatrick, Naomi L Baker, Anthony Penington, Peter G Farlie, Tiong Yang Tan
Pierre Robin Sequence (PRS) is usually classified into syndromic and nonsyndromic groups, with a further subclassification of the nonsyndromic group into isolated PRS and PRS with additional anomalies (PRS-Plus). The aim of this research is to provide an accurate phenotypic characterisation of nonsyndromic PRS, specifically the PRS-Plus subgroup. We sought to examine the frequency of sequence variants in previously defined conserved noncoding elements (CNEs) in the putative enhancer region upstream of SOX9, the regulation of which has been associated with PRS phenotypes...
November 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27879259/unexpected-role-for-p19ink4d-in-post-transcriptional-regulation-of-gata1-and-modulation-of-human-terminal-erythropoiesis
#2
Xu Han, Jieying Zhang, Yuanliang Peng, Minyuan Peng, Xiao Chen, Huiyong Chen, Jianhui Song, Xiao Hu, Mao Ye, Jianglin Li, Vijay G Sankaran, Christopher D Hillyer, Narla Mohandas, Xiuli An, Jing Liu
Terminal erythroid differentiation is tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. We show here that p19(INK4d), a member of CDKI family, is abundantly expressed in erythroblasts and that p19(INK4d) knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27861570/hmga2-moderately-increases-fetal-hemoglobin-expression-in-human-adult-erythroblasts
#3
Jaira F de Vasconcellos, Y Terry Lee, Colleen Byrnes, Laxminath Tumburu, Antoinette Rabel, Jeffery L Miller
Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with beta-hemoglobin disorders. Previous studies showed that let-7 microRNAs (miRNAs) are highly regulated in erythroid cells during the fetal-to-adult developmental transition, and that targeting let-7 mediated the up-regulation of HbF to greater than 30% of the total globin levels in human adult cultured erythroblasts. HMGA2 is a member of the high-mobility group A family of proteins and a validated target of the let-7 family of miRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27821551/senp1-drives-hypoxia-induced-polycythemia-via-gata1-and-bcl-xl-in-subjects-with-monge-s-disease
#4
Priti Azad, Huiwen W Zhao, Pedro J Cabrales, Roy Ronen, Dan Zhou, Orit Poulsen, Otto Appenzeller, Yu Hsin Hsiao, Vineet Bafna, Gabriel G Haddad
In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge's disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold)...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27815426/gata1-deficient-dendritic-cells-display-impaired-ccl21-dependent-migration-toward-lymph-nodes-due-to-reduced-levels-of-polysialic-acid
#5
Maaike R Scheenstra, Iris M De Cuyper, Filipe Branco-Madeira, Pieter de Bleser, Mirjam Kool, Marjolein Meinders, Mark Hoogenboezem, Erik Mul, Monika C Wolkers, Fiamma Salerno, Benjamin Nota, Yvan Saeys, Sjoerd Klarenbeek, Wilfred F J van IJcken, Hamida Hammad, Sjaak Philipsen, Timo K van den Berg, Taco W Kuijpers, Bart N Lambrecht, Laura Gutiérrez
Dendritic cells (DCs) play a pivotal role in the regulation of the immune response. DC development and activation is finely orchestrated through transcriptional programs. GATA1 transcription factor is required for murine DC development, and data suggest that it might be involved in the fine-tuning of the life span and function of activated DCs. We generated DC-specific Gata1 knockout mice (Gata1-KO(DC)), which presented a 20% reduction of splenic DCs, partially explained by enhanced apoptosis. RNA sequencing analysis revealed a number of deregulated genes involved in cell survival, migration, and function...
November 4, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27748371/estrogen-promotes-megakaryocyte-polyploidization-via-estrogen-receptor-beta-mediated-transcription-of-gata1
#6
C Du, Y Xu, K Yang, S Chen, X Wang, S Wang, C Wang, M Shen, F Chen, M Chen, D Zeng, F Li, T Wang, F Wang, J Zhao, G Ai, T Cheng, Y Su, J Wang
Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte differentiation and its deficiency will lead to megakaryoblastic leukemia. Here, we show that estrogen can dose-dependently promote megakaryocyte polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant up-regulation of GATA1...
October 17, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27709778/liver-fibrosis-with-hypereosinophilia-causing-transient-abnormal-myelopoiesis
#7
Shunsuke Minakata, Naoki Sakata, Norihisa Wada, Yuhei Konishi, Satoshi Marutani, Takuji Enya, Hidenori Nakagawa, Hiroshi Wada, Tsukasa Takemura
Transient abnormal myelopoesis is mostly self-resolving and has a good prognosis, but some patients subsequently die of liver fibrosis. We report the case of an infant with Down syndrome who developed life-threatening liver fibrosis at the same time as the blasts were about to disappear. This patient also had a marked increase in eosinophils, which were possibly harboring a GATA1 mutation and were expressing a high level of platelet-derived growth factor-B mRNA; these may have been involved in the development of liver fibrosis...
October 6, 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27708057/systematic-mapping-of-functional-enhancer-promoter-connections-with-crispr-interference
#8
Charles P Fulco, Mathias Munschauer, Rockwell Anyoha, Glen Munson, Sharon R Grossman, Elizabeth M Perez, Michael Kane, Brian Cleary, Eric S Lander, Jesse M Engreitz
Gene expression in mammals is regulated by noncoding elements that can affect physiology and disease, yet the functions and target genes of most noncoding elements remain unknown. We present a high-throughput approach that uses clustered regularly interspaced short palindromic repeats (CRISPR) interference (CRISPRi) to discover regulatory elements and identify their target genes. We assess >1 megabase of sequence in the vicinity of two essential transcription factors, MYC and GATA1, and identify nine distal enhancers that control gene expression and cellular proliferation...
November 11, 2016: Science
https://www.readbyqxmd.com/read/27693117/distinct-and-overlapping-dnmt1-interactions-with-multiple-transcription-factors-in-erythroid-cells-evidence-for-co-repressor-functions
#9
Dimitris N Papageorgiou, Elena Karkoulia, Alexandra Amaral-Psarris, Pavel Burda, Katarzyna Kolodziej, Jeroen Demmers, Jörg Bungert, Tomas Stopka, John Strouboulis
DNMT1 is the maintenance DNA methyltransferase shown to be essential for embryonic development and cellular growth and differentiation in many somatic tissues in mammals. Increasing evidence has also suggested a role for DNMT1 in repressing gene expression through interactions with specific transcription factors. Previously, we identified DNMT1 as an interacting partner of the TR2/TR4 nuclear receptor heterodimer in erythroid cells, implicated in the developmental silencing of fetal β-type globin genes in the adult stage of human erythropoiesis...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27667142/a-neonate-with-a-unique-non-down-syndrome-transient-proliferative-megakaryoblastic-disease
#10
Eline J M Bertrums, Arjan Buijs, Martine van Grotel, Natasja Dors, Jasmijn D E de Rooij, Valerie de Haas, Sanne Hopman, Marjolijn C J Jongmans, C M Zwaan, Marry M van den Heuvel-Eibrink
Transient myeloproliferative disorder (TMD) is a leukemia type that occurs typically in newborns. In Down syndrome, TMD is referred to as transient abnormal myelopoiesis (TAM).(32) Recently, transientness has also been reported in acute myeloid leukemia patients with germline trisomy 21 mosaicism, and even in cases with somatic trisomy 21, with or without GATA1 mutations. TMD cases without trisomy 21 are rare, and recurrent genetic aberrations that aid in clinical decision-making are scarcely described. We describe here a TMD patient without trisomy 21 or GATA1 mutation in whom single-nucleotide polymorphism analysis of leukemic blasts revealed a novel combined submicroscopic deletion (5q31...
September 26, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27633730/pioneer-factors-and-atp-dependent-chromatin-remodeling-factors-interact-dynamically-a-new-perspective-multiple-transcription-factors-can-effect-chromatin-pioneer-functions-through-dynamic-interactions-with-atp-dependent-chromatin-remodeling-factors
#11
Erin E Swinstead, Ville Paakinaho, Diego M Presman, Gordon L Hager
Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co-activators, co-repressors, multiple TFs, histone-modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering role...
September 16, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27553977/total-saponins-of-panaxnotoginseng-promotes-lymphangiogenesis-by-activation-vegf-c-expression-of-lymphatic-endothelial-cells
#12
Jinlong Li, Yan Chen, Li Zhang, Lianping Xing, Hao Xu, Yongjun Wang, Qi Shi, Qianqian Liang
ETHNOPHARMACOLOGICAL RELEVANCE: Lymphatic system plays an important role in maintaining the fluid homeostasis and normal immune responses, anatomic or functional obstruction of which leads to lymphedema, and treatments for therapeutic lymphangiogenesis are efficiency for secondary lymphedema. Total saponins of panaxnotoginseng (PNS) are a mixture isolated from Panaxnotoginseng (Burkill) F.H.Chen, which has been used as traditional Chinese medicine in China for treatment of cardio- and cerebro-vascular diseases...
December 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27550323/towards-rna-repair-of-diamond-blackfan-anemia-hematopoietic-stem-cells
#13
Diane D'Allard, Johnson Liu
Diamond Blackfan anemia (DBA) is a well known inherited bone marrow failure syndrome mostly caused by mutations in ribosomal protein (RP) genes but also rarely in the hematopoietic transcription factor gene, <i>GATA1</i>, or <i>TSR2</i>, a ribosomal protein (Rps26) chaperone gene. About 25% of patients have heterozygous mutations in the <i>RPS19</i> gene, which leads to haploinsufficiency of Rps19 protein in most cases. However, some <i>RPS19</i> missense mutations appear to act in a dominant negative fashion...
August 22, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27520307/ak048794-maintains-the-mouse-embryonic-stem-cell-pluripotency-by-functioning-as-an-mirna-sponge-for-mir-592
#14
Yang Zhou, Qing-Song Dai, Shi-Chang Zhu, Yue-Hua Han, Hai-Long Han, Bo Zhao, Rong-Rong Gao, Jun Zhang, Jing Zhang
MiR-592 has been identified as a neural-enriched microRNA, plays an important role in mNPCs differentiation, could induce astrogliogenesis differentiation arrest or/and enhance neurogenesis in vitro Previous studies showed that long noncoding RNAs (lncRNAs) were involved in the neuronal development and activity. To investigate the role of miR-592 in neurogenesis, we described the expression profile of lncRNAs in miR-592 knockout mouse embryonic stem cells (mESCs) and the corresponding normal mESCs by microarray...
October 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27510823/transient-abnormal-myelopoiesis-and-aml-in-down-syndrome-an-update
#15
REVIEW
Neha Bhatnagar, Laure Nizery, Oliver Tunstall, Paresh Vyas, Irene Roberts
Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is preceded by a transient neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in the key haematopoietic transcription factor gene GATA1. These mutations are found in almost one third of DS neonates and are frequently clinically and haematologcially 'silent'...
October 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/27471498/protective-vaccination-against-blood-stage-malaria-of-plasmodium-chabaudi-differential-gene-expression-in-the-liver-of-balb-c-mice-toward-the-end-of-crisis-phase
#16
Saleh A Al-Quraishy, Mohamed A Dkhil, Abdel-Azeem A Abdel-Baki, Denis Delic, Frank Wunderlich
Protective vaccination induces self-healing of otherwise fatal blood-stage malaria of Plasmodium chabaudi in female Balb/c mice. To trace processes critically involved in self-healing, the liver, an effector against blood-stage malaria, is analyzed for possible changes of its transcriptome in vaccination-protected in comparison to non-protected mice toward the end of the crisis phase. Gene expression microarray analyses reveal that vaccination does not affect constitutive expression of mRNA and lincRNA. However, malaria induces significant (p < 0...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27463948/inherited-platelet-dysfunction-and-hematopoietic-transcription-factor-mutations
#17
Natthapol Songdej, A Koneti Rao
Transcription factors (TFs) are proteins that bind to specific DNA sequences and regulate expression of genes. The molecular and genetic mechanisms in most patients with inherited platelet dysfunction are unknown. There is now increasing evidence that mutations in hematopoietic TFs are an important underlying cause for the defects in platelet production, morphology, and function. The hematopoietic TFs implicated in the patients with impaired platelet function include Runt related TF 1 (RUNX1), Fli-1 proto-oncogene, ETS TF (FLI1), GATA-binding protein 1 (GATA1), and growth factor independent 1B transcriptional repressor (GFI1B)...
July 27, 2016: Platelets
https://www.readbyqxmd.com/read/27442953/advances-in-understanding-the-mechanisms-of-erythropoiesis-in-homeostasis-and-disease
#18
REVIEW
Raymond Liang, Saghi Ghaffari
Anaemia or decreased blood haemoglobin is the most common blood disorder often characterized by reduced red blood cell (RBC) numbers. RBCs are produced from differentiation and commitment of haematopoietic stem cells to the erythroid lineage by a process called erythropoiesis. Coordination of erythropoietin receptor signalling with several erythroid transcription factors including GATA1 is essential for this process. A number of additional players that are critical for RBC production have been identified in recent years...
September 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27411635/early-myeloid-lineage-choice-is-not-initiated-by-random-pu-1-to-gata1-protein-ratios
#19
Philipp S Hoppe, Michael Schwarzfischer, Dirk Loeffler, Konstantinos D Kokkaliaris, Oliver Hilsenbeck, Nadine Moritz, Max Endele, Adam Filipczyk, Adriana Gambardella, Nouraiz Ahmed, Martin Etzrodt, Daniel L Coutu, Michael A Rieger, Carsten Marr, Michael K Strasser, Bernhard Schauberger, Ingo Burtscher, Olga Ermakova, Antje Bürger, Heiko Lickert, Claus Nerlov, Fabian J Theis, Timm Schroeder
The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described as being expressed in uncommitted cell populations. This led to the assumption that lineage choice is cell-intrinsically initiated and determined by stochastic switches of randomly fluctuating cross-antagonistic transcription factors. However, this hypothesis was developed on the basis of RNA expression data from snapshot and/or population-averaged analyses...
July 13, 2016: Nature
https://www.readbyqxmd.com/read/27353457/gata1-mutations-in-a-cohort-of-malaysian-children-with-down-syndrome-associated-myeloid-disorder
#20
Su Han Lum, Soo Sin Choong, Shekhar Krishnan, Zulqarnain Mohamed, Hany Ariffin
INTRODUCTION: Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum...
June 2016: Singapore Medical Journal
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