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https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#1
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28069743/derepression-of-the-dna-methylation-machinery-of-gata1-gene-triggers-the-differentiation-cue-for-erythropoiesis
#2
Lei Yu, Jun Takai, Akihito Otsuki, Fumiki Katsuoka, Mikiko Suzuki, Saori Katayama, Masahiro Nezu, James Douglas Engel, Takashi Moriguchi, Masayuki Yamamoto
GATA1 is a critical regulator of erythropoiesis. While the mechanisms underlying the high-level expression of GATA1 in maturing erythroid cells have been studied extensively, the initial activation of the Gata1 gene in early hematopoietic progenitors remains to be elucidated. We previously identified a hematopoietic stem and progenitor cell (HSPC)-specific silencer element (the Gata1 methylation determining region; G1MDR) that recruits DNA methyltransferase 1 (Dnmt1) and provokes the methylation of the Gata1 gene enhancer...
January 9, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28063190/prognostic-impact-of-specific-molecular-profiles-in-pediatric-acute-megakaryoblastic-leukemia-in-non-down-syndrome
#3
Yusuke Hara, Norio Shiba, Kentaro Ohki, Ken Tabuchi, Genki Yamato, Myoung-Ja Park, Daisuke Tomizawa, Akitoshi Kinoshita, Akira Shimada, Hirokazu Arakawa, Akiko M Saito, Nobutaka Kiyokawa, Akio Tawa, Keizo Horibe, Takashi Taga, Souichi Adachi, Tomohiko Taki, Yasuhide Hayashi
Pediatric acute megakaryoblastic leukemia with non-Down syndrome (AMKL) is a unique subtype of acute myeloid leukemia (AML). Novel CBFA2T3-GLIS2 and NUP98-KDM5A fusions recurrently found in AMKL were recently reported as poor prognostic factors. However, their detailed clinical and molecular characteristics in patients treated with recent improved therapies remain uncertain. We analyzed molecular features of 44 AMKL patients treated on two recent Japanese AML protocols, the AML99 and AML-05 trials. We identified CBFA2T3-GLIS2, NUP98-KDM5A, RBM15-MKL1, and KMT2A rearrangements in 12 (27%), 4 (9%), 2 (5%), and 3 (7%) patients, respectively...
January 7, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28057738/a-population-of-hematopoietic-stem-cells-derives-from-gata4-expressing-progenitors-located-in-the-placenta-and-lateral-mesoderm-of-mice
#4
Ana Cañete, Rita Carmona, Laura Ariza, Maria Jose Sanchez, Anabel Rojas, Ramon Muñoz-Chápuli
GATA transcription factors are expressed in mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at E7.5, becoming restricted to the septum transversum by E10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFP mouse line. We found a substantial number of YFP+ hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28028114/distinct-gata1-point-mutations-in-monozygotic-twins-with-down-syndrome-and-transient-abnormal-myelopoiesis-from-a-triplet-pregnancy-a-case-report-and-review-of-literature
#5
Liqun Yin, Mark A Lovell, Michael L Wilson, Qi Wei, Xiayuan Liang
OBJECTIVES: Down syndrome (DS)-associated transient abnormal myelopoiesis (TAM) or acute megakaryoblastic leukemia (AMKL) in monozygotic twins is exceedingly rare and has not been well characterized. METHODS: We describe a unique case of monozygotic twins with simultaneous TAM from a triplet pregnancy at 34 weeks' gestation. Previously reported cases of TAM and DS-AMKL in monozygotic twins have been reviewed to compare with our cases. The current concept of a sequential multistep process in leukemogenesis and disease evolution of TAM into DS-AMKL through the collaboration among trisomy 21, GATA1, and other gene mutations is also reviewed...
December 27, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28002765/developmental-toxicity-of-2-4-dichlorophenoxyacetic-acid-in-zebrafish-embryos
#6
Kang Li, Jia-Qi Wu, Ling-Ling Jiang, Li-Zhen Shen, Jian-Ying Li, Zhi-Heng He, Ping Wei, Zhuo Lv, Ming-Fang He
2,4-Dichlorophenoxyacetic acid (2,4-D) is widely used in agriculture as herbicide/pesticide, plant growth regulator and fruit preservative agent. It progressively accumulates in the environment including surface water, air and soil. It could be detected in human food and urine, which poses great risk to the living organisms. In the present study, we investigated the developmental toxicity of 2,4-D on zebrafish (Danio rerio) embryo. 2,4-D exposure significantly decreased both the survival rate (LC50 = 46...
December 10, 2016: Chemosphere
https://www.readbyqxmd.com/read/27956603/uhrf1-controls-the-self-renewal-versus-differentiation-of-hematopoietic-stem-cells-by-epigenetically-regulating-the-cell-division-modes
#7
Jingyao Zhao, Xufeng Chen, Guangrong Song, Jiali Zhang, Haifeng Liu, Xiaolong Liu
Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate. However, how individual HSC makes the decision between self-renewal and differentiation remains largely unknown. Here we report that ablation of the key epigenetic regulator Uhrf1 in the hematopoietic system depletes the HSC pool, leading to hematopoietic failure and lethality. Uhrf1-deficient HSCs display normal survival and proliferation, yet undergo erythroid-biased differentiation at the expense of self-renewal capacity. Notably, Uhrf1 is required for the establishment of DNA methylation patterns of erythroid-specific genes during HSC division...
December 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27927101/development-of-erythroid-progenitors-under-erythropoietin-stimulation-in-xenopus-laevis-larval-liver
#8
Takehito Okui, Sakiko Hosozawa, Satoka Kohama, Shingo Fujiyama, Shun Maekawa, Hiroshi Muto, Takashi Kato
Erythroid progenitors that respond to erythropoietin (Epo) are present in the liver of adult Xenopus laevis. However, cells responding to Epo in the larval liver and through the metamorphosis period under hepatic remodeling have not been characterized. In this study, tadpoles were staged using the tables of Nieuwkoop and Faber (NF). Liver cells from pre- (NF56) or post- (NF66) metamorphic stage were cultured in the presence of Epo. β2-globin mRNA expression peaked at day 7 after the start of culture. Larval β2-globin was highly expressed in NF56-derived cells, while adult β2-globinwas detected in those of NF66...
December 2016: Zoological Science
https://www.readbyqxmd.com/read/27920635/clinical-and-molecular-characterisation-of-children-with-pierre-robin-sequence-and-additional-anomalies
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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...
November 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
#16
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
#17
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
#18
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
#19
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
#20
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
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