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https://www.readbyqxmd.com/read/28645106/phorbol-esters-dppa-dpa-promote-furin-expression-involving-transcription-factor-cebp%C3%AE-in-neuronal-cells
#1
Jing-Si Zha, Bing-Lin Zhu, Lu Liu, Yu-Jie Lai, Yan Long, Xiao-Tong Hu, Xiao-Juan Deng, Xue-Feng Wang, Zhen Yan, Guo-Jun Chen
Using high-throughput small molecule screening targeting furin gene, we identified that phorbol esters dPPA (12-Deoxyphorbol 13-phenylacetate 20-acetate) and dPA (12-Deoxyphorbol 13-acetate) significantly increased furin protein and mRNA expression in SH-SY5Y cells. This effect was prevented by PKC (protein kinase C) inhibitor calphostin C but not Ro318220, suggesting that the C1 domain, rather than the catalytic domain of PKC plays an important role. Luciferase assay revealed that nucleotides -7925 to -7426 were sufficient to mediate dPPA/dPA enhancement of furin P1 promoter activity...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624204/crispr-cas9-directed-reassignment-of-the-gata1-initiation-codon-in-k562-cells-to-recapitulate-aml-in-down-syndrome
#2
Kevin M Bloh, Pawel A Bialk, Anilkumar Gopalakrishnapillai, E Anders Kolb, Eric B Kmiec
Using a CRISPR/Cas9 system, we have reengineered a translational start site in the GATA1 gene in K562 cells. This mutation accounts largely for the onset of myeloid leukemia in Down syndrome (ML-DS). For this reengineering, we utilized CRISPR/Cas9 to generate mammalian cell lines that express truncated versions of the Gata1s protein similar to that seen in ML-DS, as determined by analyzing specific genetic alterations resulting from CRISPR/Cas9 cleavage. During this work, 73 cell lines were clonally expanded, with allelic variance analyzed...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622305/the-thrombopoietin-mpl-axis-is-activated-in-the-gata1-low-mouse-model-of-myelofibrosis-and-is-associated-with-a-defective-rps14-signature
#3
M Zingariello, L Sancillo, F Martelli, F Ciaffoni, M Marra, L Varricchio, R A Rana, C Zhao, J D Crispino, A R Migliaccio
Myelofibrosis (MF) is characterized by hyperactivation of thrombopoietin (TPO) signaling, which induces a RPS14 deficiency that de-regulates GATA1 in megakaryocytes by hampering its mRNA translation. As mice carrying the hypomorphic Gata1(low) mutation, which reduces the levels of Gata1 mRNA in megakaryocytes, develop MF, we investigated whether the TPO axis is hyperactive in this model. Gata1(low) mice contained two times more Tpo mRNA in liver and TPO in plasma than wild-type littermates. Furthermore, Gata1(low) LSKs expressed levels of Mpl mRNA (five times greater than normal) and protein (two times lower than normal) similar to those expressed by LSKs from TPO-treated wild-type mice...
June 16, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28596438/lost-in-translation-rp-and-gata1-mutations-in-dba
#4
Kathleen M Sakamoto
No abstract text is available yet for this article.
June 8, 2017: Blood
https://www.readbyqxmd.com/read/28584082/whole-organism-cellular-gene-expression-atlas-reveals-conserved-cell-types-in-the-ventral-nerve-cord-of-platynereis-dumerilii
#5
Hernando Martínez Vergara, Paola Yanina Bertucci, Peter Hantz, Maria Antonietta Tosches, Kaia Achim, Pavel Vopalensky, Detlev Arendt
The comparative study of cell types is a powerful approach toward deciphering animal evolution. To avoid selection biases, however, comparisons ideally involve all cell types present in a multicellular organism. Here, we use image registration and a newly developed "Profiling by Signal Probability Mapping" algorithm to generate a cellular resolution 3D expression atlas for an entire animal. We investigate three-segmented young worms of the marine annelid Platynereis dumerilii, with a rich diversity of differentiated cells present in relatively low number...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28553927/erythropoietin-signaling-regulates-heme-biosynthesis
#6
Jacky Chung, Johannes G Wittig, Alireza Ghamari, Manami Maeda, Tamara A Dailey, Hector Bergonia, Martin D Kafina, Emma E Coughlin, Catherine E Minogue, Alexander S Hebert, Liangtao Li, Jerry Kaplan, Harvey F Lodish, Daniel E Bauer, Stuart H Orkin, Alan B Cantor, Takahiro Maeda, John D Phillips, Joshua J Coon, David J Pagliarini, Harry A Dailey, Barry H Paw
Heme is required for survival of all cells, and in most eukaryotes, is produced through a series of eight enzymatic reactions. Although heme production is critical for many cellular processes, how it is coupled to cellular differentiation is unknown. Here, using zebrafish, murine, and human models, we show that erythropoietin (EPO) signaling, together with the GATA1 transcriptional target, AKAP10, regulates heme biosynthesis during erythropoiesis at the outer mitochondrial membrane. This integrated pathway culminates with the direct phosphorylation of the crucial heme biosynthetic enzyme, ferrochelatase (FECH) by protein kinase A (PKA)...
May 29, 2017: ELife
https://www.readbyqxmd.com/read/28550189/gata1-erythroid-specific-regulation-of-sec23b-expression-and-its-implication-in-the-pathogenesis-of-congenital-dyserythropoietic-anemia-type-ii
#7
Roberta Russo, Immacolata Andolfo, Antonella Gambale, Gianluca De Rosa, Francesco Manna, Alessandra Arillo, Farooq Wandroo, Maria Grazia Bisconte, Achille Iolascon
No abstract text is available yet for this article.
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#8
Shuiling Jin, Hairui Su, Ngoc-Tung Tran, Jing Song, Sydney S Lu, Ying Li, Suming Huang, Omar Abdel-Wahab, Yanyan Liu, Xinyang Zhao
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2. Mutations in SF3B1 are associated with 80% cases of refractory anemia with ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most frequently mutated site among mutations on SF3B1. Yet the molecular mechanisms on how mutations of splicing factors lead to defective erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding protein, RBM15, stronger than the wild type SF3B1 protein in co-immunoprecipitation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28522827/involvement-of-gata1-and-sp3-in-the-activation-of-the-murine-sting-gene-promoter-in-nih3t3-cells
#9
Yan-Yan Xu, Rui Jin, Guo-Ping Zhou, Hua-Guo Xu
Stimulator of Interferon Gene (STING) is a key mediator of innate immune signaling. STING plays a pivotal role in the pathogenesis of many diseases including infectious diseases, auto-immune diseases and cancer. Many studies have been carried out recently in the field of STING-regulated pathway, however, rarely of transcriptional mechanisms. To characterize the murine STING (mSTING) promoter, we cloned a series of different nucleotide sequences of the 5'-flanking region of the mSTING gene. Transient transfection of promoter-reporter recombinant plasmids and luciferase assay illustrated the region (-77/+177) relative to the transcription start site (TSS) of the mSTING gene was sufficient for full promoter activity...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#10
Ivan Krivega, Ann Dean
Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28500845/hematopoietic-transcription-factors-and-differential-cofactor-binding-regulate-prkacb-isoform-expression
#11
Olga N Kuvardina, Stefanie Herkt, Annekarin Meyer, Lucas Schneider, Jasmin Yillah, Nicole Kohrs, Halvard Bonig, Erhard Seifried, Carsten Müller-Tidow, Jörn Lausen
Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28457011/diagnosis-of-inherited-platelet-disorders-on-a-blood-smear-a-tool-to-facilitate-worldwide-diagnosis-of-platelet-disorders
#12
A Greinacher, A Pecci, S Kunishima, K Althaus, P Nurden, C L Balduini, T Bakchoul
Essentials There are many hereditary platelet disorders (HPD) but diagnosing these is challenging. We provide a method to diagnose several HPDs using standard blood smears requiring < 100 µL blood. By this approach, the underlying cause of HPD was characterized in ~25-30% of referred individuals. The method facilitates diagnosis of HPD for patients of all ages around the world. SUMMARY: Background Many hereditary thrombocytopenias and/or platelet function disorders have been identified, but diagnosis of these conditions remains challenging...
April 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28446464/trf-mir-1280-suppresses-stem-cell-like-cells-and-metastasis-in-colorectal-cancer
#13
Bingqing Huang, Huipeng Yang, Xixi Cheng, Dan Wang, Shuyu Fu, Wencui Shen, Qi Zhang, Lijuan Zhang, Zhenyi Xue, Yan Li, Yurong Da, Qing Yang, Zesong Li, Li Liu, Liang Qiao, Ying Kong, Zhi Yao, Peng Zhao, Min Li, Rongxin Zhang
Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR-1280, a 17-bp fragment derived from tRNA(Leu) and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer. Ectopic expression of tRF/miR-1280 reduced cell proliferation and colony formation, whereas its suppression reversed these effects...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28418072/myb-gata1-fusion-promotes-basophilic-leukaemia-involvement-of-interleukin-33-and-nerve-growth-factor-receptors
#14
Stéphane Ducassou, Valérie Prouzet-Mauléon, Marie-Céline Deau, Philippe Brunet de la Grange, Bruno Cardinaud, Hayssam Soueidan, Cathy Quelen, Pierre Brousset, Jean-Max Pasquet, François Moreau-Gaudry, Michel Arock, François-Xavier Mahon, Eric Lippert
Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloblastic leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation generating an MYB-GATA1 fusion gene in male infants with ABL. To better understand its role, the chimeric MYB-GATA1 transcription factor was expressed in CD34-positive haematopoietic progenitors, which were transplanted into immunodeficient mice. Cells expressing MYB-GATA1 showed increased expression of markers of immaturity (CD34), of granulocytic lineage (CD33 and CD117), and of basophilic differentiation (CD203c and FcϵRI)...
April 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28416505/hematopoietic-transcription-factor-mutations-important-players-in-inherited-platelet-defects
#15
REVIEW
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 defects are unknown. There is now increasing evidence that mutations in hematopoietic TFs are an important underlying cause for defects in platelet production, morphology, and function. The hematopoietic TFs implicated in patients with impaired platelet function and number include runt-related transcription factor 1, Fli-1 proto-oncogene, E-twenty-six (ETS) transcription factor (friend leukemia integration 1), GATA-binding protein 1, growth factor independent 1B transcriptional repressor, ETS variant 6, ecotropic viral integration site 1, and homeobox A11...
May 25, 2017: Blood
https://www.readbyqxmd.com/read/28410882/epo-reprograms-the-epigenome-of-erythroid-cells
#16
Andrea A Perreault, Mary Lauren Benton, Mark J Koury, Stephen J Brandt, Bryan J Venters
The hormone erythropoietin (Epo) is required for erythropoiesis, yet its molecular mechanism of action remains poorly understood, particularly with respect to chromatin dynamics. To investigate how Epo modulates the erythroid epigenome, we performed epigenetic profiling using an ex vivo murine cell system that undergoes synchronous erythroid maturation in response to Epo stimulation. Our findings define the repertoire of Epo-modulated enhancers, illuminating a new facet of Epo signaling. First, a large number of enhancers rapidly responded to Epo stimulation, revealing a cis-regulatory network of Epo-responsive enhancers...
July 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28377399/molecular-convergence-in-ex-vivo-models-of-diamond-blackfan-anemia
#17
Kelly A O'Brien, Jason E Farrar, Adrianna Vlachos, Stacie M Anderson, Crystiana A Tsujiura, Jens Lichtenberg, Lionel Blanc, Eva Atsidaftos, Abdel Elkahloun, Xiuli An, Steven R Ellis, Jeffery M Lipton, David M Bodine
Diamond Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by erythroid hypoplasia, usually without perturbation of other hematopoietic lineages. Approximately 65% of DBA patients with autosomal dominant inheritance have heterozygous mutations or deletions in ribosomal protein (RP) genes while <1% of patients with X-linked inheritance have been identified with mutations in the transcription factor GATA1 Erythroid cells from patients with DBA have not been well characterized and the mechanisms underlying the erythroid specific effects of either RP or GATA1 associated DBA remain unclear...
April 4, 2017: Blood
https://www.readbyqxmd.com/read/28358362/deletion-of-stk40-impairs-definitive-erythropoiesis-in-the-mouse-fetal-liver
#18
Lina Wang, Hongyao Yu, Hui Cheng, Ke He, Zhuoqing Fang, Laixiang Ge, Tao Cheng, Ying Jin
The serine threonine kinase Stk40 has been shown to involve in mouse embryonic stem cell differentiation, pulmonary maturation and adipocyte differentiation. Here we report that targeted deletion of Stk40 leads to fetal liver hypoplasia and anemia in the mouse embryo. The reduction of erythrocytes in the fetal liver is accompanied by increased apoptosis and compromised erythroid maturation. Stk40(-/-) fetal liver cells have significantly reduced colony-forming units (CFUs) capable of erythroid differentiation, including burst forming unit-erythroid, CFU-erythroid (CFU-E), and CFU-granulocyte, erythrocyte, megakaryocyte and macrophage, but not CFU-granulocyte/macrophages...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28340113/gata1-is-a-sensitive-and-specific-nuclear-marker-for-erythroid-and-megakaryocytic-lineages
#19
Winston Y Lee, Olga K Weinberg, Geraldine S Pinkus
Objectives: GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods: Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders...
April 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28338218/evaluation-of-targeted-exome-sequencing-for-28-protein-based-blood-group-systems-including-the-homologous-gene-systems-for-blood-group-genotyping
#20
Elizna M Schoeman, Genghis H Lopez, Eunike C McGowan, Glenda M Millard, Helen O'Brien, Eileen V Roulis, Yew-Wah Liew, Jacqueline R Martin, Kelli A McGrath, Tanya Powley, Robert L Flower, Catherine A Hyland
BACKGROUND: Blood group single nucleotide polymorphism genotyping probes for a limited range of polymorphisms. This study investigated whether massively parallel sequencing (also known as next-generation sequencing), with a targeted exome strategy, provides an extended blood group genotype and the extent to which massively parallel sequencing correctly genotypes in homologous gene systems, such as RH and MNS. STUDY DESIGN AND METHODS: Donor samples (n = 28) that were extensively phenotyped and genotyped using single nucleotide polymorphism typing, were analyzed using the TruSight One Sequencing Panel and MiSeq platform...
April 2017: Transfusion
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