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Kdm1a

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https://www.readbyqxmd.com/read/29656462/kdm1a-regulated-the-osteo-dentinogenic-differentiation-process-of-the-stem-cells-of-the-apical-papilla-via-binding-with-plod2
#1
Lijun Wang, Haoqing Yang, Xiao Lin, Yangyang Cao, Peipei Gao, Ying Zheng, Zhipeng Fan
OBJECTIVES: Dental tissue-derived mesenchymal stem cells (MSCs)-mediated pulp-dentin regeneration is considered a potential approach for the regeneration of damaged teeth. Enhancing MSC-mediated pulp-dentin regeneration is based on an understanding of the molecular mechanisms underlying directed cell differentiation process. Histone demethylation enzyme, lysine demethylase 1A (KDM1A) can regulate the differentiation of some MSCs, but its role in dental tissue-derived MSCs is unclear. MATERIAL AND METHODS: We obtained SCAPs from immature teeth...
April 15, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29619118/epigenetic-modifications-in-kdm-lysine-demethylases-associate-with-survival-of-early-stage-nsclc
#2
Yongyue Wei, Junya Liang, Ruyang Zhang, Yichen Guo, Sipeng Shen, Li Su, Xihong Lin, Sebastian Moran, Åslaug Helland, Maria M Bjaanæs, Anna Karlsson, Maria Planck, Manel Esteller, Thomas Fleischer, Johan Staaf, Yang Zhao, Feng Chen, David C Christiani
Background: KDM lysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations in KDM genes and their roles in lung cancer survival. Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites in KDM genes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29618580/oxidative-stress-inhibits-healthy-adipose-expansion-through-suppression-of-srebf1-mediated-lipogenic-pathway
#3
Yosuke Okuno, Atsunori Fukuhara, Erika Hashimoto, Hironori Kobayashi, Sachiko Kobayashi, Michio Otsuki, Iichiro Shimomura
Recent studies have emphasized the association of adipose oxidative stress (Fat ROS) with the pathogenesis of metabolic disorders in obesity. However, the causal roles of Fat ROS in metabolic disturbances in vivo remain unclear because no mouse model has been available in which oxidative stress is manipulated targeting adipocytes. In this research, we generated two models of Fat ROS-manipulated mice and evaluated the metabolic features in diet-induced obesity. Fat ROS-eliminated mice in which Cat and Sod1 were overexpressed in adipocytes exhibited adipose expansion with decreased ectopic lipid accumulation and improved insulin sensitivity...
April 4, 2018: Diabetes
https://www.readbyqxmd.com/read/29581704/targeting-histone-demethylase-lsd1-kdm1a-in-neurodegenerative-diseases
#4
Susanna Ambrosio, Barbara Majello
The autophagy-lysosome pathway sustains cellular homeostasis and is a protective mechanism against neurodegenerative diseases. Recent findings highlight the role of the histone demethylases LSD1/LDM1A as a pivotal regulator of autophagy process, by controlling the mTORC1 cascade, in neuroblastoma cells. LSD1 binds to the promoter region of the SESN2 gene, where LSD1-mediated demethylation leads to the accumulation of repressive histone marks that maintain SESN2 expression at low levels. LSD1 depletion results in enhanced SESN2 expression and consequently mTORC1 inhibition, thereby triggering the induction of autophagy...
2018: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/29559475/germline-mutations-in-lysine-specific-demethylase-1-lsd1-kdm1a-confer-susceptibility-to-multiple-myeloma
#5
Xiaomu Wei, M Nieves Calvo-Vidal, Siwei Chen, Gang Wu, Maria V Revuelta, Jian Sun, Jinghui Zhang, Michael F Walsh, Kim E Nichols, Vijai Joseph, Carrie Snyder, Celine M Vachon, James D McKay, Shu-Ping Wang, David S Jayabalan, Lauren M Jacobs, Dina Becirovic, Rosalie G Waller, Mykyta Artomov, Agnes Viale, Jayeshkumar Patel, Jude M Phillip, Selina Chen-Kiang, Karen Curtin, Mohamed Salama, Djordje Atanackovic, Ruben Niesvizky, Ola Landgren, Susan L Slager, Lucy A Godley, Jane Churpek, Judy E Garber, Kenneth C Anderson, Mark J Daly, Robert G Roeder, Charles Dumontet, Henry T Lynch, Charles G Mullighan, Nicola J Camp, Kenneth Offit, Robert J Klein, Haiyuan Yu, Leandro Cerchietti, Steven M Lipkin
Given the frequent and largely incurable occurrence of multiple myeloma (MM), identification of germline genetic mutations that predispose cells to MM may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell. Here we identified familial and early-onset MM kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29555846/pias%C3%AE-controls-stability-and-facilitates-sumo-2-conjugation-to-corest-family-of-transcriptional-corepressors
#6
Julián Esteban Sáez, Cristian Arredondo, Carlos Rivera, María Estela Andrés
CoREST family of transcriptional corepressors regulates gene expression and cell fate determination during development. CoREST corepressors recruit with different affinity the histone demethylase LSD1 (KDM1A) and the deacetylases HDAC1/2 to repress with variable strength the expression of target genes. CoREST protein levels are differentially regulated during cell fate decisions and in mature tissues. However, regulatory mechanisms of CoREST corepressors at the protein level have not been studied. Here, we report that CoREST (CoREST1, RCOR1) and its homologs CoREST2 (RCOR2) and CoREST3 (RCOR3) interact with PIASγ, a SUMO-E3 ligase...
March 19, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29528362/histone-3-lysine-4-9-and-27-demethylases-expression-profile-in-fertilized-and-cloned-bovine-and-porcine-embryos
#7
Werner Giehl Glanzner, Vitor Braga Rissi, Mariana Priotto de Macedo, Lady Katerine Serrano Mujica, Karina Gutierrez, Alessandra Bridi, João Ricardo Malheiros de Souza, Paulo Bayard Dias Gonçalves, Vilceu Bordignon
Epigenetic modifications in the C-terminal domain of histones coordinate important events during early development including embryo genome activation (EGA) and cell differentiation. In this study, the mRNA expression profile of the main lysine demethylases (KDMs) acting on the lysine 4 (H3K4), 9 (H3K9) and 27 (H3K27) of the histone H3 was determined at pre-, during and post- EGA stages of bovine and porcine embryos produced by in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT). In IVF embryos, mRNA abundance of most KDMs revealed a bell-shaped profile with peak expression around the EGA period, i...
March 8, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29502954/ory-1001-a-potent-and-selective-covalent-kdm1a-inhibitor-for-the-treatment-of-acute-leukemia
#8
Tamara Maes, Cristina Mascaró, Iñigo Tirapu, Angels Estiarte, Filippo Ciceri, Serena Lunardi, Nathalie Guibourt, Alvaro Perdones, Michele M P Lufino, Tim C P Somervaille, Dan H Wiseman, Cihangir Duy, Ari Melnick, Christophe Willekens, Alberto Ortega, Marc Martinell, Nuria Valls, Guido Kurz, Matthew Fyfe, Julio Cesar Castro-Palomino, Carlos Buesa
The lysine-specific demethylase KDM1A is a key regulator of stem cell potential in acute myeloid leukemia (AML). ORY-1001 is a highly potent and selective KDM1A inhibitor that induces H3K4me2 accumulation on KDM1A target genes, blast differentiation, and reduction of leukemic stem cell capacity in AML. ORY-1001 exhibits potent synergy with standard-of-care drugs and selective epigenetic inhibitors, reduces growth of an AML xenograft model, and extends survival in a mouse PDX (patient-derived xenograft) model of T cell acute leukemia...
February 23, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29404406/an-mll4-compass-lsd1-epigenetic-axis-governs-enhancer-function-and-pluripotency-transition-in-embryonic-stem-cells
#9
Kaixiang Cao, Clayton K Collings, Marc A Morgan, Stacy A Marshall, Emily J Rendleman, Patrick A Ozark, Edwin R Smith, Ali Shilatifard
Chromatin regulators control cellular differentiation by orchestrating dynamic developmental gene expression programs, and hence, malfunctions in the regulation of chromatin state contribute to both developmental disorders and disease state. Mll4 (Kmt2d), a member of the COMPASS (COMplex of Proteins ASsociated with Set1) protein family that implements histone H3 lysine 4 monomethylation (H3K4me1) at enhancers, is essential for embryonic development and functions as a pancancer tumor suppressor. We define the roles of Mll4/COMPASS and its catalytic activity in the maintenance and exit of ground-state pluripotency in murine embryonic stem cells (ESCs)...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29371665/lsd1-regulates-skeletal-muscle-regeneration-and-directs-the-fate-of-satellite-cells
#10
Milica Tosic, Anita Allen, Dominica Willmann, Christoph Lepper, Johnny Kim, Delphine Duteil, Roland Schüle
Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes...
January 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339137/oxygen-induced-alterations-in-the-expression-of-chromatin-modifying-enzymes-and-the-transcriptional-regulation-of-imprinted-genes
#11
William M Skiles, Avery Kester, Jane H Pryor, Mark E Westhusin, Michael C Golding, Charles R Long
Embryo culture and assisted reproductive technologies have been associated with a disproportionately high number of epigenetic abnormalities in the resulting offspring. However, the mechanisms by which these techniques influence the epigenome remain poorly defined. In this study, we evaluated the capacity of oxygen concentration to influence the transcriptional control of a selection of key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen concentrations modulated the transcriptional regulation of the TET family of enzymes, as well as the de novo methyltransferase Dnmt3a...
June 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29207083/a-type-2-diabetes-associated-snp-in-kcnq1-rs163184-modulates-the-binding-activity-of-the-locus-for-sp3-and-lsd1-kdm1a-potentially-affecting-cdkn1c-expression
#12
Masaki Hiramoto, Haruhide Udagawa, Naoko Ishibashi, Eri Takahashi, Yasushi Kaburagi, Keisuke Miyazawa, Nobuaki Funahashi, Takao Nammo, Kazuki Yasuda
Although genome-wide association studies have shown that potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is one of the genes that is most significantly associated with type 2 diabetes mellitus (T2DM), functionally annotating disease-associated single nucleotide polymorphisms (SNPs) remains a challenge. Recently, our group described a novel strategy to identify proteins that bind to SNP-containing loci in an allele-specific manner. The present study successfully applied this strategy to investigate rs163184, a T2DM susceptibility SNP located in the intronic region of KCNQ1...
February 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29156705/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#13
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#14
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130516/microrna-329-inhibits-cell-proliferation-and-tumor-growth-while-facilitates-apoptosis-via-negative-regulation-of-kdm1a-in-gastric-cancer
#15
Lisheng Cai, Qiuxian Chen, Shunyong Fang, Mingqiao Lian, Mingzhi Cai
Altered expression of microRNA (miRNA) is strongly implicated in gastric cancer (GC). Here, we demonstrated a decreased expression of miRNA-329 in GC. Then we explored the regulatory mechanisms responsible for its effect on GC cells. GC tissues and their adjacent non-tumor tissues were collected. Complete follow-up was updated. A series of inhibitors, mimics, and siRNA against KDM1A were introduced to validate regulatory mechanisms for miR-497 and KDM1A in BGC-823 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were employed for evaluating the expressions of miRNA-329, KDM1A, H3K4me1, and H3K4me2...
April 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29075615/pharmacologic-targeting-of-chromatin-modulators-as-therapeutics-of-acute-myeloid-leukemia
#16
REVIEW
Rui Lu, Gang Greg Wang
Acute myeloid leukemia (AML), a common hematological cancer of myeloid lineage cells, generally exhibits poor prognosis in the clinic and demands new treatment options. Recently, direct sequencing of samples from human AMLs and pre-leukemic diseases has unveiled their mutational landscapes and significantly advanced the molecular understanding of AML pathogenesis. The newly identified recurrent mutations frequently "hit" genes encoding epigenetic modulators, a wide range of chromatin-modifying enzymes and regulatory factors involved in gene expression regulation, supporting aberration of chromatin structure and epigenetic modification as a main oncogenic mechanism and cancer-initiating event...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29030483/rbpj-cbf1-interacts-with-l3mbtl3-mbt1-to-promote-repression-of-notch-signaling-via-histone-demethylase-kdm1a-lsd1
#17
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
November 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28993646/lsd1-protects-against-hippocampal-and-cortical-neurodegeneration
#18
Michael A Christopher, Dexter A Myrick, Benjamin G Barwick, Amanda K Engstrom, Kirsten A Porter-Stransky, Jeremy M Boss, David Weinshenker, Allan I Levey, David J Katz
To investigate the mechanisms that maintain differentiated cells, here we inducibly delete the histone demethylase LSD1/KDM1A in adult mice. Loss of LSD1 leads to paralysis, along with widespread hippocampus and cortex neurodegeneration, and learning and memory defects. We focus on the hippocampus neuronal cell death, as well as the potential link between LSD1 and human neurodegenerative disease and find that loss of LSD1 induces transcription changes in common neurodegeneration pathways, along with the re-activation of stem cell genes, in the degenerating hippocampus...
October 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28974232/the-stem-cell-factor-sall4-is-an-essential-transcriptional-regulator-in-mixed-lineage-leukemia-rearranged-leukemogenesis
#19
Lina Yang, Li Liu, Hong Gao, Jaya Pratap Pinnamaneni, Deepthi Sanagasetti, Vivek P Singh, Kai Wang, Megumi Mathison, Qianzi Zhang, Fengju Chen, Qianxing Mo, Todd Rosengart, Jianchang Yang
BACKGROUND: The stem cell factor spalt-like transcription factor 4 (SALL4) plays important roles in normal hematopoiesis and also in leukemogenesis. We previously reported that SALL4 exerts its effect by recruiting important epigenetic factors such as DNA methyltransferases DNMT1 and lysine-specific demethylase 1 (LSD1/KDM1A). Both of these proteins are critically involved in mixed lineage leukemia (MLL)-rearranged (MLL-r) leukemia, which has a very poor clinical prognosis. Recently, SALL4 has been further linked to the functions of MLL and its target gene homeobox A9 (HOXA9)...
October 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28931919/ror%C3%AE-2-requires-lsd1-to-enhance-tumor-progression-in-breast-cancer
#20
Kyeongkyu Kim, Ji Min Lee, Young Suk Yu, Hyunkyung Kim, Hye Jin Nam, Hyeong-Gon Moon, Dong-Young Noh, Keun Il Kim, Sungsoon Fang, Sung Hee Baek
Retinoic acid-related orphan receptor α (RORα) regulates diverse physiological processes, including inflammatory responses, lipid metabolism, circadian rhythm, and cancer biology. RORα has four different isoforms which have distinct N-terminal domains but share identical DNA binding domain and ligand binding domain in human. However, lack of specific antibody against each RORα isoform makes biochemical studies on each RORα isoform remain unclear. Here, we generate RORα2-specific antibody and characterize the role of RORα2 in promoting tumor progression in breast cancer...
September 20, 2017: Scientific Reports
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