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https://www.readbyqxmd.com/read/28811072/evolution-of-hemoglobin-loci-and-their-regulatory-elements
#1
REVIEW
Sjaak Philipsen, Ross C Hardison
Across the expanse of vertebrate evolution, each species produces multiple forms of hemoglobin in erythroid cells at appropriate times and in the proper amounts. The multiple hemoglobins are encoded in two globin gene clusters in almost all species. One globin gene cluster, linked to the gene NPRL3, is preserved in all vertebrates, including a gene cluster encoding the highly divergent globins from jawless vertebrates. This preservation of synteny may reflect the presence of a powerful enhancer of globin gene expression in the NPRL3 gene...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#2
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28736882/the-clinical-significance-of-monitoring-the-expression-of-the-sil-tal1-fusion-gene-in-t-cell-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#3
X Zhao, Y Hong, Y Qin, Y Xu, Y Chang, Y Wang, X Zhang, L Xu, X Huang
INTRODUCTION: SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL). However, whether this fusion gene might be used as a reliable marker of minimal residual disease (MRD) following allogeneic stem cell transplantation (allo-HSCT) remains unknown METHODS: The clinical data of consecutive 29 patients with T-ALL who received allo-HSCT were collected. Their MRD were evaluated by SIL-TAL1, Wilms' tumor 1 (WT1) expression, and the leukemia-associated immunophenotype (LAIP) ...
July 24, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28700586/systematic-identification-and-characterization-of-regulatory-elements-derived-from-human-endogenous-retroviruses
#4
Jumpei Ito, Ryota Sugimoto, Hirofumi Nakaoka, Shiro Yamada, Tetsuaki Kimura, Takahide Hayano, Ituro Inoue
Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs)...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28685891/specification-of-neurotransmitter-identity-by-tal1-in-thalamic-nuclei
#5
Bumwhee Lee, Myungsin Lee, Somang Song, Linh Duc Loi, Duc Tri Lam, Jaeseung Yoon, Kwanghee Baek, David J Curtis, Yongsu Jeong
BACKGROUND: The neurons contributing to thalamic nuclei are derived from at least two distinct progenitor domains, the caudal (cTH) and rostral (rTH) population of thalamic progenitors. These neural compartments exhibit unique neurogenic patterns and the molecular mechanisms underlying the acquisition of neurotransmitter identity remain largely unclear. RESULTS: T-cell acute lymphocytic leukemia protein 1 (Tal1) was expressed in the early postmitotic cells in the rTH domain, and its expression was maintained in mature thalamic neurons in the ventrolateral geniculate nucleus (vLG) and the intergeniculate leaflet (IGL)...
July 7, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28679996/transcriptional-regulation-of-erythropoiesis
#6
Tohru Fujiwara
Hematopoietic cell differentiation is regulated by various lineage-specific transcription factors. In the context of erythroid differentiation, the importance of GATA-1 has been unequivocally demonstrated by cell-based ex vivo assays, as well as knockout mouse models and rare patients with anemias. GATA-1 regulates the expression of erythroid-related genes, such as globins and genes involved in heme biosynthesis, by recognizing the DNA binding consensus sequence [(A/T) GATA (A/G)] through dual zinc finger motifs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28671693/transcriptomic-analysis-of-purified-human-cortical-microglia-reveals-age-associated-changes
#7
Thais F Galatro, Inge R Holtman, Antonio M Lerario, Ilia D Vainchtein, Nieske Brouwer, Paula R Sola, Mariana M Veras, Tulio F Pereira, Renata E P Leite, Thomas Möller, Paul D Wes, Mari C Sogayar, Jon D Laman, Wilfred den Dunnen, Carlos A Pasqualucci, Sueli M Oba-Shinjo, Erik W G M Boddeke, Suely K N Marie, Bart J L Eggen
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fcγ and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle...
August 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28671688/the-genomic-landscape-of-pediatric-and-young-adult-t-lineage-acute-lymphoblastic-leukemia
#8
Yu Liu, John Easton, Ying Shao, Jamie Maciaszek, Zhaoming Wang, Mark R Wilkinson, Kelly McCastlain, Michael Edmonson, Stanley B Pounds, Lei Shi, Xin Zhou, Xiaotu Ma, Edgar Sioson, Yongjin Li, Michael Rusch, Pankaj Gupta, Deqing Pei, Cheng Cheng, Malcolm A Smith, Jaime Guidry Auvil, Daniela S Gerhard, Mary V Relling, Naomi J Winick, Andrew J Carroll, Nyla A Heerema, Elizabeth Raetz, Meenakshi Devidas, Cheryl L Willman, Richard C Harvey, William L Carroll, Kimberly P Dunsmore, Stuart S Winter, Brent L Wood, Brian P Sorrentino, James R Downing, Mignon L Loh, Stephen P Hunger, Jinghui Zhang, Charles G Mullighan
Genetic alterations that activate NOTCH1 signaling and T cell transcription factors, coupled with inactivation of the INK4/ARF tumor suppressors, are hallmarks of T-lineage acute lymphoblastic leukemia (T-ALL), but detailed genome-wide sequencing of large T-ALL cohorts has not been carried out. Using integrated genomic analysis of 264 T-ALL cases, we identified 106 putative driver genes, half of which had not previously been described in childhood T-ALL (for example, CCND3, CTCF, MYB, SMARCA4, ZFP36L2 and MYCN)...
August 2017: Nature Genetics
https://www.readbyqxmd.com/read/28652130/tal1-as-a-master-oncogenic-transcription-factor-in-t-cell-acute-lymphoblastic-leukemia
#9
REVIEW
Takaomi Sanda, Wei Zhong Leong
In hematopoietic cell development, the transcriptional program is strictly regulated in a lineage- and stage-specific manner that requires a number of transcription factors to work in a cascade or in a loop, in addition to interactions with nonhematopoietic cells in the microenvironment. Disruption of the transcriptional program alters the cellular state and may predispose cells to the acquisition of genetic abnormalities. Early studies have shown that proteins that promote cell differentiation often serve as tumor suppressors, whereas inhibitors of those proteins act as oncogenes in the context of acute leukemia...
June 24, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28606225/-clinical-characteristics-and-prognostic-analysis-of-children-and-adolescents-over-10-years-of-age-with-acute-lymphoblastic-leukemia
#10
Jun Wu, Ai-Dong Lu, Le-Ping Zhang
OBJECTIVE: To explore the clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL). METHODS: A total of 86 newly diagnosed ALL children and adolescents over 10 years of age (62 cases of B-ALL and 24 cases of T-ALL) were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#11
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
October 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#12
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/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#13
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
#14
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/28410882/epo-reprograms-the-epigenome-of-erythroid-cells
#15
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/28352301/functional-overexpression-of-genes-involved-in-erythritol-synthesis-in-the-yeast-yarrowia-lipolytica
#16
Aleksandra M Mirończuk, Anna Biegalska, Adam Dobrowolski
BACKGROUND: Erythritol, a four-carbon polyol synthesized by microorganisms as an osmoprotectant, is a natural sweetener produced on an industrial scale for decades. Despite the fact that the yeast Yarrowia lipolytica has been reported since the 1970s as an erythritol producer, the metabolic pathway of this polyol has never been characterized. It was shown that erythritol synthesis in yeast occurs via the pentose phosphate pathway (PPP). The oleaginous yeast Y. lipolytica is a good host for converting inexpensive glycerol into a value-added product such as erythritol...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28299656/roles-of-the-runx1-enhancer-in-normal-hematopoiesis-and-leukemogenesis
#17
Wei-Siang Liau, Phuong Cao Thi Ngoc, Takaomi Sanda
Enhancers are regulatory elements in genomic DNA that contain specific sequence motifs that are bound by DNA-binding transcription factors. The activity of enhancers is tightly regulated in an integrated and combinatorial manner, thus yielding complex patterns of transcription in different tissues. Identifying enhancers is crucial to understanding the physiological and pathogenic roles of their target genes. The RUNX1 intronic enhancer, eR1, acts in cis to regulate RUNX1 gene expression in hematopoietic stem cells (HSCs) and hemogenic endothelial cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28244490/the-rna-binding-protein-qki5-regulates-primary-mir-124-1-processing-via-a-distal-rna-motif-during-erythropoiesis
#18
Fang Wang, Wei Song, Hongmei Zhao, Yanni Ma, Yuxia Li, Di Zhai, Jingnan Pi, Yanmin Si, Jiayue Xu, Lei Dong, Rui Su, Mengmeng Zhang, Yong Zhu, Xiaoxia Ren, Fei Miao, Wenjie Liu, Feng Li, Junwu Zhang, Aibin He, Ge Shan, Jingyi Hui, Linfang Wang, Jia Yu
MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation...
March 2017: Cell Research
https://www.readbyqxmd.com/read/28216155/forced-fog1-expression-in-erythroleukemia-cells-induction-of-erythroid-genes-and-repression-of-myelo-lymphoid-transcription-factor-pu-1
#19
Tohru Fujiwara, Katsuyuki Sasaki, Kei Saito, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
The transcription factor GATA-1-interacting protein Friend of GATA-1 (FOG1) is essential for proper transcriptional activation and repression of GATA-1 target genes; yet, the mechanisms by which FOG1 exerts its activating and repressing functions remain unknown. Forced FOG1 expression in human K562 erythroleukemia cells induced the expression of erythroid genes (SLC4A1, globins) but repressed that of GATA-2 and PU.1. A quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated increased GATA-1 chromatin occupancy at both FOG1-activated as well as FOG1-repressed gene loci...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28181081/genetic-improvement-of-xylose-metabolism-by-enhancing-the-expression-of-pentose-phosphate-pathway-genes-in-saccharomyces-cerevisiae-ir-2-for-high-temperature-ethanol-production
#20
Yosuke Kobayashi, Takehiko Sahara, Toshihiro Suzuki, Saori Kamachi, Akinori Matsushika, Tamotsu Hoshino, Satoru Ohgiya, Yoichi Kamagata, Kazuhiro E Fujimori
The pentose phosphate pathway (PPP) plays an important role in the efficiency of xylose fermentation during cellulosic ethanol production. In simultaneous saccharification and co-fermentation (SSCF), the optimal temperature for cellulase hydrolysis of lignocellulose is much higher than that of fermentation. Successful use of SSCF requires optimization of the expression of PPP genes at elevated temperatures. This study examined the combinatorial expression of PPP genes at high temperature. The results revealed that over-expression of TAL1 and TKL1 in Saccharomyces cerevisiae (S...
February 8, 2017: Journal of Industrial Microbiology & Biotechnology
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