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https://www.readbyqxmd.com/read/29884215/crebbp-ep300-bromodomains-are-critical-to-sustain-the-gata1-myc-regulatory-axis-in-proliferation
#1
Veronica Garcia-Carpizo, Sergio Ruiz-Llorente, Jacinto Sarmentero, Osvaldo Graña-Castro, David G Pisano, Maria J Barrero
BACKGROUND: The reported antitumor activity of the BET family bromodomain inhibitors has prompted the development of inhibitors against other bromodomains. However, the human genome encodes more than 60 different bromodomains and most of them remain unexplored. RESULTS: We report that the bromodomains of the histone acetyltransferases CREBBP/EP300 are critical to sustain the proliferation of human leukemia and lymphoma cell lines. EP300 is very abundant at super-enhancers in K562 and is coincident with sites of GATA1 and MYC occupancy...
June 8, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29846281/identification-of-a-novel-mutation-in-the-sec23b-gene-associated-with-congenital-dyserythropoietic-anemia-type-ii-through-the-use-of-next-generation-sequencing-panel-in-an-undiagnosed-case-of-nonimmune-hereditary-hemolytic-anemia
#2
Sultan Aydin Koker, Tuba H Karapinar, Yeşim Oymak, Paola Bianchi, Elisa Fermo, Salih Gozmen, Canan Vergin
Congenital dyserythropoietic anemias (CDAs) are rare hereditary blood disorders characterized by ineffective erythropoiesis, hemolysis, and erythroblast morphologic abnormalities in the bone marrow. The 3 main types of CDA, I to III, and variant types of CDA, IV-VIII, have been described. The causative genes have been identified as CDAN1, C15ORF41, SEC23B, KIF23, KLF1, and GATA1. CDA type II is the most frequent form. Typical symptoms are jaundice, hepatosplenomegaly, mild-to-severe normocytic anemia, and inadequate reticulocyte response...
May 25, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29843710/gene-expression-of-the-liver-of-vaccination-protected-mice-in-response-to-early-patent-infections-of-plasmodium-chabaudi-blood-stage-malaria
#3
Saleh Al-Quraishy, Mohamed A Dkhil, E M Al-Shaebi, Abdel-Azeem S Abdel-Baki, Marcos J Araúzo-Bravo, Denis Delic, Frank Wunderlich
BACKGROUND: The role of the liver for survival of blood-stage malaria is only poorly understood. In experimental blood-stage malaria with Plasmodium chabaudi, protective vaccination induces healing and, thus, survival of otherwise lethal infections. This model is appropriate to study the role of the liver in vaccination-induced survival of blood-stage malaria. METHODS: Female Balb/c mice were vaccinated with a non-infectious vaccine consisting of plasma membranes isolated in the form of erythrocyte ghosts from P...
May 29, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29800703/perioperative-inhibition-of-%C3%AE-adrenergic-andcox2-signaling-in-a-clinical-trial-in-breast-cancer-patients-improves-tumor-ki-67-expression-serum-cytokine-levels-and-pbmcs-transcriptome
#4
Rita Haldar, Lee Shaashua, Hagar Lavon, Yasmin A Lyons, Oded Zmora, Eran Sharon, Yehudit Birnbaum, Tanir Allweis, Anil K Sood, Iris Barshack, Steve Cole, Shamgar Ben-Eliyahu
Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n=38), we tested the combined perioperative use of the β-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4)...
May 22, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29753742/mirna-152-targets-gata1-to-regulate-erythropoiesis-in-chionodraco-hamatus
#5
Jiulin Chan, Xingxing Hu, Congcong Wang, Qianghua Xu
Chionodraco hamatus is a teleost within the suborder Notothenioidei, the members of which are known to lack functional erythrocytes with modified hematopoiesis. Hematopoiesis is an essential process during the development of animals, where it is tightly regulated by many different transcription factors, signaling proteins, chromatin modifications, and microRNAs (miRNAs). The miRNAs are known to regulate the expression of their target genes at the post-transcriptional level. However, little is known about the miRNA-mediated regulation of hematopoiesis...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29748255/disruption-of-a-gata1-binding-motif-upstream-of-xg-pbdx-abolishes-xg-a-expression-and-resolves-the-xg-blood-group-system
#6
Mattias Möller, Yan Quan Lee, Karina Vidovic, Sven Kjellström, Linda Björkman, Jill R Storry, Martin L Olsson
The Xga blood group is differentially expressed on erythrocytes from males and females. The underlying gene, PBDX , was identified already in 1994 but the molecular background for Xga expression remains undefined. This gene, now designated XG , partly resides in the pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome. By comparing calculated Xga allele frequencies in different populations to 2,612 genetic variants in the XG region, rs311103 showed the strongest correlation to the expected distribution...
May 10, 2018: Blood
https://www.readbyqxmd.com/read/29747653/inactivation-of-the-tight-junction-gene-cldn11-by-aberrant-hypermethylation-modulates-tubulins-polymerization-and-promotes-cell-migration-in-nasopharyngeal-carcinoma
#7
Hsin-Pai Li, Chen-Ching Peng, Chih-Ching Wu, Chien-Hsun Chen, Meng-Jhe Shih, Mei-Yuan Huang, Yi-Ru Lai, Yung-Li Chen, Ting-Wen Chen, Petrus Tang, Yu-Sun Chang, Kai-Ping Chang, Cheng-Lung Hsu
BACKGROUND: Aberrant hypermethylation of cellular genes is a common phenomenon to inactivate genes and promote tumorigenesis in nasopharyngeal carcinoma (NPC). METHODS: Methyl binding domain (MBD)-ChIP sequencing of NPC cells, microarray data of NPC biopsies and gene ontology analysis were conducted to identify a potential tumor suppressor gene CLDN11 that was both hypermethylated and downregulated in NPC. Bisulfite sequencing, qRT-PCR, immunohistochemistry staining of the NPC clinical samples and addition of methylation inhibitor, 5'azacytidine, in NPC cells were performed to verify the correlation between DNA hypermethylation and expression of CLDN11...
May 10, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29743870/absence-of-wdr13-gene-predisposes-mice-to-mild-social-isolation-chronic-stress-leading-to-depression-like-phenotype-associated-with-differential-expression-of-synaptic-proteins
#8
Shiladitya Mitra, Ghantasala S Sameer Kumar, B Jyothi Lakshmi, Suman Thakur, Satish Kumar
We earlier reported that the male mice lacking the Wdr13 gene ( Wdr13 -/0 ) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13 -/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29741776/skewed-megakaryopoiesis-in-human-induced-pluripotent-stem-cell-derived-haematopoietic-progenitor-cells-harbouring-calreticulin-mutations
#9
Hiraku Takei, Yoko Edahiro, Shuichi Mano, Nami Masubuchi, Yoshihisa Mizukami, Misa Imai, Soji Morishita, Kyohei Misawa, Tomonori Ochiai, Satoshi Tsuneda, Hiroshi Endo, Sou Nakamura, Koji Eto, Akimichi Ohsaka, Marito Araki, Norio Komatsu
Somatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2- and MPL-unmutated Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs. However, the roles of mutant CALR in human haematopoietic cell differentiation remain predominantly elusive. To examine the impact of the 5-base insertion mutant CALR gene (Ins5) on haematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient harbouring a CALR-Ins5 mutation and from a healthy individual (WT)...
May 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29713515/the-role-of-tal1-in-hematopoiesis-and-leukemogenesis
#10
E R Vagapova, P V Spirin, T D Lebedev, V S Prassolov
TAL1 (SCL/TAL1, T-cell acute leukemia protein 1) is a transcription factor that is involved in the process of hematopoiesis and leukemogenesis. It participates in blood cell formation, forms mesoderm in early embryogenesis, and regulates hematopoiesis in adult organisms. TAL1 is essential in maintaining the multipotency of hematopoietic stem cells (HSC) and keeping them in quiescence (stage G0). TAL1 forms complexes with various transcription factors, regulating hematopoiesis (E2A/HEB, GATA1-3, LMO1-2, Ldb1, ETO2 , RUNX1, ERG, FLI1)...
January 2018: Acta Naturae
https://www.readbyqxmd.com/read/29712898/c-ebp%C3%AE-enhances-platinum-resistance-of-ovarian-cancer-cells-by-reprogramming-h3k79-methylation
#11
Dan Liu, Xiao-Xue Zhang, Meng-Chen Li, Can-Hui Cao, Dong-Yi Wan, Bi-Xin Xi, Jia-Hong Tan, Ji Wang, Zong-Yuan Yang, Xin-Xia Feng, Fei Ye, Gang Chen, Peng Wu, Ling Xi, Hui Wang, Jian-Feng Zhou, Zuo-Hua Feng, Ding Ma, Qing-Lei Gao
Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPβ, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPβ, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner...
April 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29611379/gata1-expression-in-bcr-abl1-negative-myeloproliferative-neoplasms
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
July 2018: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29472540/exploiting-genetic-variation-to-uncover-rules-of-transcription-factor-binding-and-chromatin-accessibility
#19
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
#20
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 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 study 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
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