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https://www.readbyqxmd.com/read/29611379/gata1-expression-in-bcr-abl1-negative-myeloproliferative-neoplasms
#1
Naery Yang, Sholhui Park, Min Sun Cho, Miae Lee, Ki Sook Hong, Yeung Chul Mun, Chu Myong Seong, Hee Jin Huh, Jungwon Huh
BACKGROUND: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records...
July 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29567780/gata1s-exerts-developmental-stage-specific-effects-in-human-hematopoiesis
#2
Sofia Gialesaki, Anna Katharina Mahnken, Lena Schmid, Maurice Labuhn, Raj Bhayadia, Dirk Heckl, Jan-Henning Klusmann
No abstract text is available yet for this article.
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29563491/rna-cytosine-methylation-and-methyltransferases-mediate-chromatin-organization-and-5-azacytidine-response-and-resistance-in-leukaemia
#3
Jason X Cheng, Li Chen, Yuan Li, Adam Cloe, Ming Yue, Jiangbo Wei, Kenneth A Watanabe, Jamile M Shammo, John Anastasi, Qingxi J Shen, Richard A Larson, Chuan He, Michelle M Le Beau, James W Vardiman
The roles of RNA 5-methylcytosine (RNA:m5 C) and RNA:m5 C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure...
March 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29562644/understanding-splenomegaly-in-myelofibrosis-association-with-molecular-pathogenesis
#4
REVIEW
Moo-Kon Song, Byeong-Bae Park, Ji-Eun Uhm
Myelofibrosis (MF) is a clinical manifestation of chronic BCR-ABL1-negative chronic myeloproliferative neoplasms. Splenomegaly is one of the major clinical manifestations of MF and is directly linked to splenic extramedullary hematopoiesis (EMH). EMH is associated with abnormal trafficking patterns of clonal hematopoietic cells due to the dysregulated bone marrow (BM) microenvironment leading to progressive splenomegaly. Several recent data have emphasized the role of several cytokines for splenic EMH. Alteration of CXCL12/CXCR4 pathway could also lead to splenic EMH by migrated clonal hematopoietic cells from BM to the spleen...
March 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29547954/mbd2-cp2c-loop-drives-adult-type-globin-gene-expression-and-definitive-erythropoiesis
#5
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29481579/loss-of-full-length-gata1-expression-in-megakaryocytes-is-a-sensitive-and-specific-immunohistochemical-marker-for-the-diagnosis-of-myeloid-proliferative-disorder-related-to-down-syndrome
#6
Winston Y Lee, Olga K Weinberg, Andrew G Evans, Geraldine S Pinkus
Objectives: Myeloid proliferative disorders associated with Down syndrome (MPD-DS), including transient abnormal myelopoiesis and myeloid leukemia associated with Down syndrome (DS), harbor mutations of GATA1, a transcription factor essential for erythroid and megakaryocytic development. These mutations result in a N-terminally truncated GATA1 (GATA1s) and prohibit the production of the full-length GATA1 (GATA1f). Here, we demonstrate the utility of immunohistochemical GATA1f reactivity in diagnosing MPD-DS...
March 7, 2018: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29475801/role-of-tissue-specific-promoter-dna-methylation-in-regulating-the-human-eklf-gene
#7
Yihong Li, Dun Liu, Zhiming Li, Xinhua Zhang, Yuhua Ye, Qifa Liu, Jie Shen, Zhi Chen, Huajie Huang, Yunhao Liang, Xu Han, Jing Liu, Xiuli An, Narla Mohandas, Xiangmin Xu
Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid-specific transcription factor whose activity is essential for erythropoiesis. The underlying mechanisms for EKLF specifically restricted to erythroid cells are of great interest but remain incompletely understood. To explore the epigenetic regulation of EKLF expression by promoter DNA methylation, we investigated the methylation status of the EKLF promoter and EKLF gene expression from a panel of human tissues. We observed that erythroid-specific hypomethylation of the EKLF promoter in adult erythroid cells was positively associated with EKLF expression...
February 15, 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29472540/exploiting-genetic-variation-to-uncover-rules-of-transcription-factor-binding-and-chromatin-accessibility
#8
Vivek Behera, Perry Evans, Carolyne J Face, Nicole Hamagami, Laavanya Sankaranarayanan, Cheryl A Keller, Belinda Giardine, Kai Tan, Ross C Hardison, Junwei Shi, Gerd A Blobel
Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact of discriminatory single-nucleotide variants on TF ChIP signal enables definition at single base resolution of in vivo binding characteristics of nuclear factors GATA1, TAL1, and CTCF...
February 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29442367/no-strict-requirement-for-eosinophils-for-bone-marrow-plasma-cell-survival
#9
Alexandra Bortnick, Irene Chernova, Sean P Spencer, David Allman
Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the bone marrow (BM) in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro-survival signals to nearby plasma cells. Recent work shows that many BM plasma cells are recently generated and chiefly short-lived cells, raising the possibility that rare plasma cell-eosinophil interactions are a rate-limiting step needed to establish lasting humoral immunity...
February 14, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29435140/triplications-of-human-chromosome-21-orthologous-regions-in-mice-result-in-expansion-of-megakaryocyte-erythroid-progenitors-and-reduction-of-granulocyte-macrophage-progenitors
#10
Chunhong Liu, Tao Yu, Zhuo Xing, Xiaoling Jiang, Yichen Li, Annie Pao, Justin Mu, Paul K Wallace, George Stoica, Andrei V Bakin, Y Eugene Yu
Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s. The mouse has been used for modeling DS based on the syntenic conservation between human chromosome 21 (Hsa21) and three regions in the mouse genome located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. To assess the impact of the dosage increase of Hsa21 gene orthologs on the hematopoietic system, we characterized the related phenotype in the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ model which carries duplications spanning the entire Hsa21 orthologous regions on Mmu10, Mmu16 and Mmu17, and the Dp(10)1Yey /+; Dp(16)1Yey /+; Dp(17)1Yey/+ ; Gata1 Yeym2 model which carries a Gata1s mutation we engineered...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29417230/identification-of-megakaryocytes-as-a-target-of-advanced-glycation-end-products-in-diabetic-complications-in-bone-marrow
#11
Benfang Wang, Jianjiang Yu, Ting Wang, Ying Shen, Dandan Lin, Xin Xu, Yiqiang Wang
AIMS: To define the possible effect of diabetic conditions on megakaryocytes, the long-know precursors of platelets and lately characterized modulator of hematopoietic stem quiescence-activation transition. METHODS: Megakaryoblastic MEG-01 cell culture and TPO/SCF/IL-3-induced differentiation of human umbilical blood mononuclear cells toward megakaryocytes were used to test effects of glycated bovine serum albumin (BSA-AGEs). The ob/ob mice and streptozotocin-treated mice were used as models of hyperglycemia...
February 8, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29408805/ribonuclease-inhibitor-1-regulates-erythropoiesis-by-controlling-gata1-mrna-translation
#12
Vijaykumar Chennupati, Diogo Ft Veiga, Kendle M Maslowski, Nicola Andina, Aubry Tardivel, Eric Chi-Wang Yu, Martina Stilinovic, Cedric Simillion, Michel A Duchosal, Manfredo Quadroni, Irene Roberts, Vijay G Sankaran, H Robson MacDonald, Nicolas Fasel, Anne Angelillo-Scherrer, Pascal Schneider, Trang Hoang, Ramanjaneyulu Allam
Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anaemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anaemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor (RNH1) is an ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases...
February 6, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29400094/gata1-insufficiencies-in-primary-myelofibrosis-and-other-hematopoietic-disorders-consequences-for-therapy
#13
Te Ling, John D Crispino, Maria Zingariello, Fabrizio Martelli, Anna Rita Migliaccio
GATA1, the founding member of a family of transcription factors, plays important roles in the development of hematopoietic cells of several lineages. Although loss of GATA1 has been known to impair hematopoiesis in animal models for nearly 25 years, the link between GATA1 defects and human blood diseases has only recently been realized. Areas covered: Here the current understanding of the functions of GATA1 in normal hematopoiesis and how it is altered in disease is reviewed. GATA1 is indispensable mainly for erythroid and megakaryocyte differentiation...
February 5, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29389946/the-effect-of-histone-deacetylase-inhibitors-on-ahsp-expression
#14
Mohammad Ali Okhovat, Katayoun Ziari, Reza Ranjbaran, Negin Nikouyan
Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3...
2018: PloS One
https://www.readbyqxmd.com/read/29382819/rassf1a-uncouples-wnt-from-hippo-signalling-and-promotes-yap-mediated-differentiation-via-p73
#15
Angelos Papaspyropoulos, Leanne Bradley, Asmita Thapa, Chuen Yan Leung, Konstantinos Toskas, Delia Koennig, Dafni-Eleftheria Pefani, Cinzia Raso, Claudia Grou, Garth Hamilton, Nikola Vlahov, Anna Grawenda, Syed Haider, Jagat Chauhan, Ludovico Buti, Alexander Kanapin, Xin Lu, Francesca Buffa, Grigory Dianov, Alex von Kriegsheim, David Matallanas, Anastasia Samsonova, Magdalena Zernicka-Goetz, Eric O'Neill
Transition from pluripotency to differentiation is a pivotal yet poorly understood developmental step. Here, we show that the tumour suppressor RASSF1A is a key player driving the early specification of cell fate. RASSF1A acts as a natural barrier to stem cell self-renewal and iPS cell generation, by switching YAP from an integral component in the β-catenin-TCF pluripotency network to a key factor that promotes differentiation. We demonstrate that epigenetic regulation of the Rassf1A promoter maintains stemness by allowing a quaternary association of YAP-TEAD and β-catenin-TCF3 complexes on the Oct4 distal enhancer...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29377892/network-based-co-expression-analysis-for-exploring-the-potential-diagnostic-biomarkers-of-metastatic-melanoma
#16
Li-Xin Wang, Yang Li, Guan-Zhi Chen
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach...
2018: PloS One
https://www.readbyqxmd.com/read/29321178/transcription-factor-dependent-anti-repressive-mammalian-enhancers-exclude-h3k27me3-from-extended-genomic-domains
#17
Madhurima Saxena, Adrianna K San Roman, Nicholas K O'Neill, Rita Sulahian, Unmesh Jadhav, Ramesh A Shivdasani
Compacted chromatin and nucleosomes are known barriers to gene expression; the nature and relative importance of other transcriptional constraints remain unclear, especially at distant enhancers. Polycomb repressor complex 2 (PRC2) places the histone mark H3K27me3 predominantly at promoters, where its silencing activity is well documented. In adult tissues, enhancers lack H3K27me3, and it is unknown whether intergenic H3K27me3 deposits affect nearby genes. In primary intestinal villus cells, we identified hundreds of tissue-restricted enhancers that require the transcription factor (TF) CDX2 to prevent the incursion of H3K27me3 from adjoining areas of elevated basal marking into large well-demarcated genome domains...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29317231/the-ancient-role-for-gata2-3-transcription-factor-homolog-in-the-hemocyte-production-of-oyster
#18
Xiaorui Song, Xiaoyu Xin, Miren Dong, Weilin Wang, Lingling Wang, Linsheng Song
Hemocytes, the cellular component of invertebrate hemolymph, are essential for invertebrate immunity, but the hematopoiesis and regulation mechanism are still largely unknown. In the present study, a conserved hematopoietic transcription factor Cg-GATA2/3 was identified in Pacific oyster Crassotrea gigas, which was evolutionarily close to the vertebrate GATA1/2/3. Cg-GATA2/3 was mainly distributed in the immune organs, such as gill, hemocytes, and mantle. After Cg-GATA2/3 was interferenced by dsRNA, the mRNA expressions of hemocytes specific gene (EcSOD) and hematopoietic transcription factor (C-Myb) were all significant down-regulated, and the hemocyte renewal rates also decreased both in hemolymph and gill...
May 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29302254/terminally-differentiating-eosinophils-express-neutrophil-primary-granule-proteins-as-well-as-eosinophil-specific-granule-proteins-in-a-temporal-manner
#19
Karam Kim, Sae Mi Hwang, Sung Min Kim, Sung Woo Park, Yunjae Jung, Il Yup Chung
Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34+ cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29296843/the-severe-phenotype-of-diamond-blackfan-anemia-is-modulated-by-heat-shock-protein-70
#20
Marc Gastou, Sarah Rio, Michaël Dussiot, Narjesse Karboul, Hélène Moniz, Thierry Leblanc, Margaux Sevin, Patrick Gonin, Jérome Larghéro, Carmen Garrido, Anupama Narla, Narla Mohandas, William Vainchenker, Olivier Hermine, Eric Solary, Lydie Da Costa
Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome that exhibits an erythroid-specific phenotype. In at least 70% of cases, DBA is related to a haploinsufficient germ line mutation in a ribosomal protein (RP) gene. Additional cases have been associated with mutations in GATA1. We have previously established that the RPL11+/Mut phenotype is more severe than RPS19+/Mut phenotype because of delayed erythroid differentiation and increased apoptosis of RPL11+/Mut erythroid progenitors...
October 10, 2017: Blood Advances
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