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Utx signalling

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https://www.readbyqxmd.com/read/27602485/increasing-notch-signaling-antagonizes-prc2-mediated-silencing-to-promote-reprograming-of-germ-cells-into-neurons
#1
Stefanie Seelk, Irene Adrian-Kalchhauser, Balázs Hargitai, Martina Hajduskova, Silvia Gutnik, Baris Tursun, Rafal Ciosk
Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch...
September 7, 2016: ELife
https://www.readbyqxmd.com/read/27132888/mechanism-and-role-of-sox2-repression-in-seminoma-relevance-to-human-germline-specification
#2
Ritu Kushwaha, Nirmala Jagadish, Manjunath Kustagi, Geetu Mendiratta, Marco Seandel, Rekha Soni, James E Korkola, Venkata Thodima, Andrea Califano, George J Bosl, R S K Chaganti
Human male germ cell tumors (GCTs) are derived from primordial germ cells (PGCs). The master pluripotency regulator and neuroectodermal lineage effector transcription factor SOX2 is repressed in PGCs and the seminoma (SEM) subset of GCTs. The mechanism of SOX2 repression and its significance to GC and GCT development currently are not understood. Here, we show that SOX2 repression in SEM-derived TCam-2 cells is mediated by the Polycomb repressive complex (PcG) and the repressive H3K27me3 chromatin mark that are enriched at its promoter...
May 10, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/26450788/dual-roles-of-rnf2-in-melanoma-progression
#3
Kunal Rai, Kadir C Akdemir, Lawrence N Kwong, Petko Fiziev, Chang-Jiun Wu, Emily Z Keung, Sneha Sharma, Neha S Samant, Maura Williams, Jacob B Axelrad, Amiksha Shah, Dong Yang, Elizabeth A Grimm, Michelle C Barton, Denai R Milton, Timothy P Heffernan, James W Horner, Suhendan Ekmekcioglu, Alexander J Lazar, Jason Ernst, Lynda Chin
UNLABELLED: Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to monoubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling...
December 2015: Cancer Discovery
https://www.readbyqxmd.com/read/26306033/the-histone-demethylase-utx-promotes-brown-adipocyte-thermogenic-program-via-coordinated-regulation-of-h3k27-demethylation-and-acetylation
#4
Lin Zha, Fenfen Li, Rui Wu, Liana Artinian, Vincent Rehder, Liqing Yu, Houjie Liang, Bingzhong Xue, Hang Shi
Brown adipocytes function to dissipate energy as heat through adaptive thermogenesis. Understanding the molecular mechanisms underlying the brown fat thermogenic program may provide insights for the development of therapeutic approaches in the treatment of obesity. Most studies investigating the mechanisms underlying brown fat development focus on genetic mechanisms; little is known about the epigenetic mechanisms in this process. We have discovered that ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase for di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), plays a potential role in regulating brown adipocyte thermogenic program...
October 9, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25920016/histone-demethylase-utx-regulates-differentiation-and-mineralization-in-osteoblasts
#5
Di Yang, Hirohiko Okamura, Jumpei Teramachi, Tatsuji Haneji
Alteration of methylation status of lysine 27 on histone H3 (H3K27) associates with dramatic changes in gene expression in response to various differentiation signals. Demethylation of H3K27 is controlled by specific histone demethylases including ubiquitously transcribed tetratricopeptide repeat X chromosome (Utx). However, the role of Utx in osteoblast differentiation remains unknown. In this study, we examined whether Utx should be involved in osteoblast differentiation. Expression of Utx increased during osteoblast differentiation in MC3T3-E1 cells and primary osteoblasts...
November 2015: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/25254151/maintenance-of-cell-fates-through-acetylated-histone-and-the-histone-variant-h2a-z-in-c-elegans
#6
Yukimasa Shibata, Kiyoji Nishiwaki
Maintenance of cell fates is essential for the development and homeostasis of multicellular organisms and involves the preservation of the expression status of selector genes that control many target genes. Epigenetic marks have pivotal roles in the maintenance of gene expression status, as occurs with methylation on lysine 27 of histone H3 (H3K27me) for Hox gene regulation. In contrast, because the levels of histone acetylation decrease during the mitotic phase, acetylated histone has not been believed to contribute to the maintenance of cell fates...
2014: Worm
https://www.readbyqxmd.com/read/25225064/concurrent-alterations-in-tert-kdm6a-and-the-brca-pathway-in-bladder-cancer
#7
Michael L Nickerson, Garrett M Dancik, Kate M Im, Michael G Edwards, Sevilay Turan, Joseph Brown, Christina Ruiz-Rodriguez, Charles Owens, James C Costello, Guangwu Guo, Shirley X Tsang, Yingrui Li, Quan Zhou, Zhiming Cai, Lee E Moore, M Scott Lucia, Michael Dean, Dan Theodorescu
PURPOSE: Genetic analysis of bladder cancer has revealed a number of frequently altered genes, including frequent alterations of the telomerase (TERT) gene promoter, although few altered genes have been functionally evaluated. Our objective is to characterize alterations observed by exome sequencing and sequencing of the TERT promoter, and to examine the functional relevance of histone lysine (K)-specific demethylase 6A (KDM6A/UTX), a frequently mutated histone demethylase, in bladder cancer...
September 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/24465480/interleukin-4-mediated-15-lipoxygenase-1-trans-activation-requires-utx-recruitment-and-h3k27me3-demethylation-at-the-promoter-in-a549-cells
#8
Hongya Han, Dawei Xu, Cheng Liu, Hans-Erik Claesson, Magnus Björkholm, Jan Sjöberg
Arachidonate 15-lipoxygenase-1 (ALOX15) oxygenates polyunsaturated fatty acids and bio-membranes, generating multiple lipid signalling mediators involved in inflammation. Several lines of evidence indicate that ALOX15 activation in the respiratory tract contributes to asthma progression. Recent experimental data reveals that histone modification at the promoter plays a critical role in ALOX15 gene transcription. In the present study, we examined the status of histone H3 trimethyl-lysine 27 (H3K27me3) at the ALOX15 promoter by chromatin immunoprecipitation assay in human lung epithelial carcinoma A549 cells incubated with or without interleukin (IL)-4...
2014: PloS One
https://www.readbyqxmd.com/read/24078252/genome-wide-profiling-reveals-stimulus-specific-functions-of-p53-during-differentiation-and-dna-damage-of-human-embryonic-stem-cells
#9
Kadir C Akdemir, Abhinav K Jain, Kendra Allton, Bruce Aronow, Xueping Xu, Austin J Cooney, Wei Li, Michelle Craig Barton
How tumor suppressor p53 selectively responds to specific signals, especially in normal cells, is poorly understood. We performed genome-wide profiling of p53 chromatin interactions and target gene expression in human embryonic stem cells (hESCs) in response to early differentiation, induced by retinoic acid, versus DNA damage, caused by adriamycin. Most p53-binding sites are unique to each state and define stimulus-specific p53 responses in hESCs. Differentiation-activated p53 targets include many developmental transcription factors and, in pluripotent hESCs, are bound by OCT4 and NANOG at chromatin enriched in both H3K27me3 and H3K4me3...
January 2014: Nucleic Acids Research
https://www.readbyqxmd.com/read/23732671/-expression-of-myogenin-and-mck-genes-regulated-by-pi3k-akt-pathway
#10
Jing Li, Yun-Sheng Zhang, Ning Li, Xiao-Xiang Hu, Guo-Qing Shi, Shou-Ren Liu, Nan Liu
Many intracellular signaling pathways regulate skeletal muscle differentiation. Among them, PI3K/AKT pathway plays an important role. But the mechanisms of chromatin regulation remain unclear. In this study, the murine C2C12 myoblast cell line was used to investigate the expression of Myogenin and MCK genes during the skeletal muscle differentiation. Western blotting analysis showed that the expression of Myogenin and MCK protein was increased significantly after PI3K/AKT activator treatment for 24 h during the C2C12 cell differentiation and the expression of H3K27me3 demethylase UTX was also increased...
May 2013: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/23573229/utx-is-required-for-proper-induction-of-ectoderm-and-mesoderm-during-differentiation-of-embryonic-stem-cells
#11
Cristina Morales Torres, Anne Laugesen, Kristian Helin
Embryonic development requires chromatin remodeling for dynamic regulation of gene expression patterns to ensure silencing of pluripotent transcription factors and activation of developmental regulators. Demethylation of H3K27me3 by the histone demethylases Utx and Jmjd3 is important for the activation of lineage choice genes in response to developmental signals. To further understand the function of Utx in pluripotency and differentiation we generated Utx knockout embryonic stem cells (ESCs). Here we show that Utx is not required for the proliferation of ESCs, however, Utx contributes to the establishment of ectoderm and mesoderm in vitro...
2013: PloS One
https://www.readbyqxmd.com/read/23534949/targeting-of-nf-kappab-signaling-pathway-other-signaling-pathways-and-epigenetics-in-therapy-of-multiple-myeloma
#12
REVIEW
Ota Fuchs
Multiple myeloma (MM) remains an incurable disease, at least for the big majority of patients, in spite of the great progress with new drugs in the last years. New treatment strategies are needed to improve the outcome of patients. NF-κB activation in MM is caused by mutations in the factors involved in the NF-κB pathways contributing to their dysregulation and by signals from the bone marrow microenvironment. Agents with NF-κB inhibitory activity enhance the anti-MM effects of conventional chemotherapeutic agents...
March 1, 2013: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/23459941/the-drosophila-ortholog-of-mll3-and-mll4-trithorax-related-functions-as-a-negative-regulator-of-tissue-growth
#13
Hiroshi Kanda, Alexander Nguyen, Leslie Chen, Hideyuki Okano, Iswar K Hariharan
The human MLL genes (MLL1 to MLL4) and their Drosophila orthologs, trithorax (trx) and trithorax related (trr), encode proteins capable of methylating histone H3 on lysine 4. MLL1 and MLL2 are most similar to trx, while MLL3 and MLL4 are more closely related to trr. Several MLL genes are mutated in human cancers, but how these proteins regulate cell proliferation is not known. Here we show that trr mutant cells have a growth advantage over their wild-type neighbors and display changes in the levels of multiple proteins that regulate growth and cell division, including Notch, Capicua, and cyclin B...
May 2013: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/22949634/utx-regulates-mesoderm-differentiation-of-embryonic-stem-cells-independent-of-h3k27-demethylase-activity
#14
Chaochen Wang, Ji-Eun Lee, Young-Wook Cho, Ying Xiao, Qihuang Jin, Chengyu Liu, Kai Ge
To investigate the role of histone H3K27 demethylase UTX in embryonic stem (ES) cell differentiation, we have generated UTX knockout (KO) and enzyme-dead knock-in male ES cells. Deletion of the X-chromosome-encoded UTX gene in male ES cells markedly decreases expression of the paralogous UTY gene encoded by Y chromosome, but has no effect on global H3K27me3 level, Hox gene expression, or ES cell self-renewal. However, UTX KO cells show severe defects in mesoderm differentiation and induction of Brachyury, a transcription factor essential for mesoderm development...
September 18, 2012: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/22823977/myeloid-malignancies-mutations-models-and-management
#15
REVIEW
Anne Murati, Mandy Brecqueville, Raynier Devillier, Marie-Joelle Mozziconacci, Véronique Gelsi-Boyer, Daniel Birnbaum
Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia) and acute (acute myeloid leukemia) stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS), transcription factors (e.g. CEBPA, ETV6, RUNX1), epigenetic regulators (e...
2012: BMC Cancer
https://www.readbyqxmd.com/read/22722839/the-mutational-landscape-of-lethal-castration-resistant-prostate-cancer
#16
Catherine S Grasso, Yi-Mi Wu, Dan R Robinson, Xuhong Cao, Saravana M Dhanasekaran, Amjad P Khan, Michael J Quist, Xiaojun Jing, Robert J Lonigro, J Chad Brenner, Irfan A Asangani, Bushra Ateeq, Sang Y Chun, Javed Siddiqui, Lee Sam, Matt Anstett, Rohit Mehra, John R Prensner, Nallasivam Palanisamy, Gregory A Ryslik, Fabio Vandin, Benjamin J Raphael, Lakshmi P Kunju, Daniel R Rhodes, Kenneth J Pienta, Arul M Chinnaiyan, Scott A Tomlins
Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains and losses, including ETS gene family fusions, PTEN loss and androgen receptor (AR) amplification, which drive prostate cancer development and progression to lethal, metastatic castration-resistant prostate cancer (CRPC). However, less is known about the role of mutations. Here we sequenced the exomes of 50 lethal, heavily pre-treated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment-naive, high-grade localized prostate cancers...
July 12, 2012: Nature
https://www.readbyqxmd.com/read/22289493/chronic-myelomonocytic-leukemia-and-atypical-chronic-myeloid-leukemia-novel-pathogenetic-lesions
#17
REVIEW
Hideki Muramatsu, Hideki Makishima, Jaroslaw P Maciejewski
Chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML) are distinct, yet related, entities of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) characterized by morphologic dysplasia with accumulation of monocytes or neutrophils, respectively. Our understanding of the molecular pathogenesis of CMML and aCML has advanced, mainly due to the application of novel technologies such as array-based karyotyping and next-generation sequencing. In addition to previously known recurrent aberrations, somatic uniparental disomy affecting chromosomes 3, 4, 7, and 11 frequently occurs in CMML...
February 2012: Seminars in Oncology
https://www.readbyqxmd.com/read/21834846/the-h3k27-demethylase-utx-1-regulates-c-%C3%A2-elegans-lifespan-in-a-germline-independent-insulin-dependent-manner
#18
Travis J Maures, Eric L Greer, Anna G Hauswirth, Anne Brunet
Aging is accompanied by alterations in epigenetic marks that control chromatin states, including histone acetylation and methylation. Enzymes that reversibly affect histone marks associated with active chromatin have recently been found to regulate aging in Caenorhabditis elegans. However, relatively little is known about the importance for aging of histone marks associated with repressed chromatin. Here, we use a targeted RNAi screen in C. elegans to identify four histone demethylases that significantly regulate worm lifespan, UTX-1, RBR-2, LSD-1, and T26A5...
December 2011: Aging Cell
https://www.readbyqxmd.com/read/21803287/histone-demethylase-utx-1-regulates-c-elegans-life-span-by-targeting-the-insulin-igf-1-signaling-pathway
#19
Chunyu Jin, Jing Li, Christopher D Green, Xiaoming Yu, Xia Tang, Dali Han, Bo Xian, Dan Wang, Xinxin Huang, Xiongwen Cao, Zheng Yan, Lei Hou, Jiancheng Liu, Nicholas Shukeir, Philipp Khaitovich, Charlie D Chen, Hong Zhang, Thomas Jenuwein, Jing-Dong J Han
Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging...
August 3, 2011: Cell Metabolism
https://www.readbyqxmd.com/read/21803283/aged-worms-erase-epigenetic-history
#20
COMMENT
Victoria V Lunyak, Brian K Kennedy
Defining the molecular events that precipitate multisystem decline is an important component of aging research. In this issue, Jin et al. (2011) show that increased expression of the histone demethylase, utx-1, causes genome-wide decreases in histone H3K27 trimethylation, which includes the insulin/IGF-1 signaling (IIS) pathway that promotes aging.
August 3, 2011: Cell Metabolism
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