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https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#1
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763382/kdm2b-is-a-histone-h3k79-demethylase-and-induces-transcriptional-repression-via-sirtuin-1-mediated-chromatin-silencing
#2
Joo-Young Kang, Ji-Young Kim, Kee-Beom Kim, Jin Woo Park, Hana Cho, Ja Young Hahm, Yun-Cheol Chae, Daehwan Kim, Hyun Kook, Sangmyeong Rhee, Nam-Chul Ha, Sang-Beom Seo
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29755503/genome-wide-association-analysis-of-age-dependent-egg-weights-in-chickens
#3
Zhuang Liu, Congjiao Sun, Yiyuan Yan, Guangqi Li, Guiqin Wu, Aiqiao Liu, Ning Yang
Egg weight (EW) is an economically-important trait and displays a consecutive increase with the hen's age. Because extremely large eggs cause a range of problems in the poultry industry, we performed a genome-wide association study (GWAS) in order to identify genomic variations that are associated with EW. We utilized the Affymetrix 600 K high density SNP array in a population of 1,078 hens at seven time points from day at first egg to 80 weeks age (EW80). Results reveal that a 90 Kb genomic region (169.42 Mb ~ 169...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29751582/whole-exome-sequencing-identifies-new-host-genomic-susceptibility-factors-in-empyema-caused-by-streptococcus-pneumoniae-in-children-a-pilot-study
#4
Antonio Salas, Jacobo Pardo-Seco, Ruth Barral-Arca, Miriam Cebey-López, Alberto Gómez-Carballa, Irene Rivero-Calle, Sara Pischedda, María-José Currás-Tuala, Jorge Amigo, José Gómez-Rial, Federico Martinón-Torres
Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls...
May 3, 2018: Genes
https://www.readbyqxmd.com/read/29719716/expression-of-meis-and-hoxa11-in-dipnoan-and-teleost-fins-provides-new-insights-into-the-evolution-of-vertebrate-appendages
#5
Fernanda Langellotto, Maria Fiorentino, Elena De Felice, Luigi Caputi, Valeria Nittoli, Jean M P Joss, Paolo Sordino
Background: The concerted activity of Meis and Hoxa11 transcription factors is essential for the subdivision of tetrapod limbs into proximo-distal (PD) domains; however, little is know about the evolution of this patterning mechanism. Here, we aim to study the expression of meis and hoxa11 orthologues in the median and paired rayed fins of zebrafish and in the lobed fins of the Australian lungfish. Results: First, a late phase of expression of meis1.1 and hoxa11b in zebrafish dorsal and anal fins relates with segmentation of endochondral elements in proximal and distal radials...
2018: EvoDevo
https://www.readbyqxmd.com/read/29719258/ppm1k-regulates-hematopoiesis-and-leukemogenesis-through-cdc20-mediated-ubiquitination-of-meis1-and-p21
#6
Xiaoye Liu, Feifei Zhang, Yaping Zhang, Xie Li, Chiqi Chen, Meiyi Zhou, Zhuo Yu, Yunxia Liu, Yuzheng Zhao, Xiaoxin Hao, Yabin Tang, Liang Zhu, Ligen Liu, Li Xie, Hao Gu, Hongfang Shao, Fangzhen Xia, Chunrong Yin, Minfang Tao, Jingjing Xie, Cheng Cheng Zhang, Yi Yang, Haipeng Sun, Guo-Qiang Chen, Junke Zheng
In addition to acting as building blocks for biosynthesis, amino acids might serve as signaling regulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs). By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs), we could monitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K) promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29716922/meis1-and-meis2-expression-and-prostate-cancer-progression-a-role-for-hoxb13-binding-partners-in-metastatic-disease
#7
Raj R Bhanvadia, Calvin VanOpstall, Hannah Brechka, Nimrod S Barashi, Marc Gillard, Erin M McAuley, Juan Apiz, Gladell P Paner, Wen-Ching Chan, Jorge Andrade, Angelo Demarzo, Misop Han, Russell Z Szmulewitz, Donald J Vander Griend
PURPOSE: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS-HOX interactions in prostate cancer etiology and progression.  The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. EXPERIMENTAL DESIGN: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29592525/meis1-is-specifically-upregulated-in-kidney-myofibroblasts-during-aging-and-injury-but-is-not-required-for-kidney-homeostasis-or-fibrotic-response
#8
Monica Chang-Panesso, Farid F Kadyrov, Flavia G Machado, Ashish Kumar, Benjamin D Humphreys
The homeobox transcription factor Meis1 is required for mammalian development and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease, and tested this using cell lineage tracing and cell specific Meis1 deletion in development, aging and fibrotic disease. We observed strong expression of Meis1 in PDGFRβ positive pericytes and perivascular fibroblasts, both in adult mouse and to a lesser degree in human kidney...
March 28, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29459901/mechanisms-and-therapeutic-targets-of-cardiac-regeneration-closing-the-age-gap
#9
REVIEW
Raphael F P Castellan, Marco Meloni
While a regenerative response is limited in the mammalian adult heart, it has been recently shown that the neonatal mammalian heart possesses a marked but transient capacity for regeneration after cardiac injury, including myocardial infarction. These findings evidence that the mammalian heart still retains a regenerative capacity and highlights the concept that the expression of distinct molecular switches (that activate or inhibit cellular mechanisms regulating tissue development and regeneration) vary during different stages of life, indicating that cardiac regeneration is an age-dependent process...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29456179/the-chromatin-remodeler-bptf-activates-a-stemness-gene-expression-program-essential-for-the-maintenance-of-adult-hematopoietic-stem-cells
#10
Bowen Xu, Ling Cai, Jason M Butler, Dongliang Chen, Xiongdong Lu, David F Allison, Rui Lu, Shahin Rafii, Joel S Parker, Deyou Zheng, Gang Greg Wang
Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29432078/endogenous-tumor-suppressor-microrna-193b-therapeutic-and-prognostic-value-in-acute-myeloid-leukemia
#11
Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Döhner, Tobias Mätzig, Michelle Ng, Dirk Reinhardt, Hartmut Döhner, C Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R Keith Humphries, Michael A Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo...
April 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29396371/genome-wide-analysis-of-pdx1-target-genes-in-human-pancreatic-progenitors
#12
Xianming Wang, Michael Sterr, Ingo Burtscher, Shen Chen, Anja Hieronimus, Fausto Machicao, Harald Staiger, Hans-Ulrich Häring, Gabriele Lederer, Thomas Meitinger, Filippo M Cernilogar, Gunnar Schotta, Martin Irmler, Johannes Beckers, Martin Hrabě de Angelis, Michael Ray, Christopher V E Wright, Mostafa Bakhti, Heiko Lickert
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far...
March 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29384595/mll-rearranged-acute-myeloid-leukemia-influence-of-the-genetic-partner-in-allo-hsct-response-and-prognostic-factor-of-mll-3-region-mrna-expression
#13
Sergio Burillo-Sanz, Rosario M Morales-Camacho, Teresa Caballero-Velázquez, Estrella Carrillo, Javier Sánchez, Olga Pérez-López, Inmaculada Pérez de Soto, José González Campos, Concepción Prats-Martín, Ricardo Bernal, María Teresa Vargas
OBJECTIVE: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML). METHODS: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes...
May 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29358086/meis1-regulates-hemogenic-endothelial-generation-megakaryopoiesis-and-thrombopoiesis-in-human-pluripotent-stem-cells-by-targeting-tal1-and-fli1
#14
Hongtao Wang, Cuicui Liu, Xin Liu, Mengge Wang, Dan Wu, Jie Gao, Pei Su, Tatsutoshi Nakahata, Wen Zhou, Yuanfu Xu, Lihong Shi, Feng Ma, Jiaxi Zhou
Human pluripotent stem cells (hPSCs) provide an unlimited source for generating various kinds of functional blood cells. However, efficient strategies for generating large-scale functional blood cells from hPSCs are still lacking, and the mechanism underlying human hematopoiesis remains largely unknown. In this study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital for specification of APLNR+ mesoderm progenitors to functional hemogenic endothelial progenitors (HEPs), thereby controlling formation of hematopoietic progenitor cells (HPCs)...
February 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29317485/meis1-coordinates-cerebellar-granule-cell-development-by-regulating-pax6-transcription-bmp-signaling-and-atoh1-degradation
#15
Tomoo Owa, Shinichiro Taya, Satoshi Miyashita, Mariko Yamashita, Toma Adachi, Koyo Yamada, Miwa Yokoyama, Shogo Aida, Tomoki Nishioka, Yukiko U Inoue, Ryo Goitsuka, Takuro Nakamura, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino
Cerebellar granule cell precursors (GCPs) and granule cells (GCs) represent good models to study neuronal development. Here, we report that the transcription factor myeloid ectopic viral integration site 1 homolog (Meis1) plays pivotal roles in the regulation of mouse GC development. We found that Meis1 is expressed in GC lineage cells and astrocytes in the cerebellum during development. Targeted disruption of the Meis1 gene specifically in the GC lineage resulted in smaller cerebella with disorganized lobules...
January 31, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29296870/a-knock-in-mouse-strain-facilitates-dynamic-tracking-and-enrichment-of-meis1
#16
Ping Xiang, Wei Wei, Nicole Hofs, Jack Clemans-Gibbon, Tobias Maetzig, Courteney K Lai, Ishpreet Dhillon, Christopher May, Jens Ruschmann, Edith Schneider, Patricia Rosten, Kaiji Hu, Florian Kuchenbauer, Pamela A Hoodless, R Keith Humphries
Myeloid ecotropic viral integration site 1 (MEIS1), a HOX transcription cofactor, is a critical regulator of normal hematopoiesis, and its overexpression is implicated in a wide range of leukemias. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) gene-editing system, we generated a knock-in transgenic mouse line in which a green fluorescent protein (GFP) reporter and a hemagglutinin (HA) epitope tag are inserted near the translational start site of endogenous Meis1 ...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29240787/brd3-4-inhibition-and-flt3-ligand-deprivation-target-pathways-that-are-essential-for-the-survival-of-human-mll-af9-leukemic-cells
#17
Marco Carretta, Annet Z Brouwers-Vos, Matthieu Bosman, Sarah J Horton, Joost H A Martens, Edo Vellenga, Jan Jacob Schuringa
In the present work we aimed to identify targetable signaling networks in human MLL-AF9 leukemias. We show that MLL-AF9 cells critically depend on FLT3-ligand induced pathways as well as on BRD3/4 for their survival. We evaluated the in vitro and in vivo efficacy of the BRD3/4 inhibitor I-BET151 in various human MLL-AF9 (primary) models and patient samples and analyzed the transcriptome changes following treatment. To further understand the mode of action of BRD3/4 inhibition, we performed ChIP-seq experiments on the MLL-AF9 complex in THP1 cells and compared it to RNA-seq data of I-BET151 treated cells...
2017: PloS One
https://www.readbyqxmd.com/read/29217774/micro-ribonucleic-acid-155-is-a-direct-target-of-meis1-but-not-a-driver-in-acute-myeloid-leukemia
#18
Edith Schneider, Anna Staffas, Linda Röhner, Erik D Malmberg, Arghavan Ashouri, Kathrin Krowiorz, Nicole Pochert, Christina Miller, Stella Yuan Wei, Laleh Arabanian, Christian Buske, Hartmut Döhner, Lars Bullinger, Linda Fogelstrand, Michael Heuser, Konstanze Döhner, Ping Xiang, Jens Ruschmann, Oleh I Petriv, Alireza Heravi-Moussavi, Carl L Hansen, Martin Hirst, R Keith Humphries, Arefeh Rouhi, Lars Palmqvist, Florian Kuchenbauer
Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected...
February 2018: Haematologica
https://www.readbyqxmd.com/read/29217648/the-interaction-of-enl-with-paf1-mitigates-polycomb-silencing-and-facilitates-murine-leukemogenesis
#19
Katrin Hetzner, Maria-Paz Garcia-Cuellar, Christian Büttner, Robert K Slany
Eleven-nineteen leukemia (ENL) is a chromatin reader present in complexes stimulating transcriptional elongation. It is fused to mixed-lineage leukemia (MLL) in leukemia, and missense mutations have been identified in Wilms tumor and acute myeloid leukemia. Here we demonstrate that ENL overcomes polycomb silencing through recruitment of PAF1 via the conserved YEATS domain, which recognizes acetylated histone H3. PAF1 was responsible for antirepressive activities of ENL in vitro, and it determined the transforming potential of MLL-ENL...
February 8, 2018: Blood
https://www.readbyqxmd.com/read/29194616/comparative-analysis-of-single-cell-rna-sequencing-data-from-mouse-spermatogonial-and-mesenchymal-stem-cells-to-identify-differentially-expressed-genes-and-transcriptional-regulators-of-germline-cells
#20
Sajjad Sisakhtnezhad, Parvin Heshmati
Identifying effective internal factors for regulating germline commitment during development and for maintaining spermatogonial stem cells (SSCs) self-renewal is important to understand the molecular basis of spermatogenesis process, and to develop new protocols for the production of the germline cells from other cell sources. Therefore, this study was designed to investigate single-cell RNA-sequencing data for identification of differentially expressed genes (DEGs) in 12 mouse-derived single SSCs (mSSCs) in compare with 16 mouse-derived single mesenchymal stem cells...
December 1, 2017: Journal of Cellular Physiology
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