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https://www.readbyqxmd.com/read/29605177/distinct-proteomic-transcriptomic-and-epigenetic-stress-responses-in-dorsal-and-ventral-hippocampus
#1
Amalia Floriou-Servou, Lukas von Ziegler, Luzia Stalder, Oliver Sturman, Mattia Privitera, Anahita Rassi, Alessio Cremonesi, Beat Thöny, Johannes Bohacek
BACKGROUND: Acutely stressful experiences can trigger neuropsychiatric disorders and impair cognitive processes by altering hippocampal function. Although the intrinsic organization of the hippocampus is highly conserved throughout its long dorsal-ventral axis, the dorsal (anterior) hippocampus mediates spatial navigation and memory formation, whereas the ventral (posterior) hippocampus is involved in emotion regulation. To understand the molecular consequences of stress, detailed genome-wide screens are necessary and need to distinguish between dorsal and ventral hippocampal regions...
February 16, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29594337/therapeutic-potential-of-gsk-j4-a-histone-demethylase-kdm6b-jmjd3-inhibitor-for-acute-myeloid-leukemia
#2
Yunan Li, Mingying Zhang, Mengyao Sheng, Peng Zhang, Zizhen Chen, Wen Xing, Jie Bai, Tao Cheng, Feng-Chun Yang, Yuan Zhou
PURPOSE: Acute myeloid leukemia (AML) is a heterogeneous disease with poor outcomes. Despite increased evidence shows that dysregulation of histone modification contributes to AML, specific drugs targeting key histone modulators are not applied in the clinical treatment of AML. Here, we investigated whether targeting KDM6B, the demethylase of tri-methylated histone H3 lysine 27 (H3K27me3), has a therapeutic potential for AML. METHODS: A KDM6B-specific inhibitor, GSK-J4, was applied to treat the primary cells from AML patients and AML cell lines in vitro and in vivo...
March 28, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29528362/histone-3-lysine-4-9-and-27-demethylases-expression-profile-in-fertilized-and-cloned-bovine-and-porcine-embryos
#3
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/29477140/aurka-suppresses-leukemic-thp-1-cell-differentiation-through-inhibition-of-the-kdm6b-pathway
#4
Jin Woo Park, Hana Cho, Hyein Oh, Ji-Young Kim, Sang-Beom Seo
Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region...
February 23, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29422491/targeting-estrogen-receptor-beta-er%C3%AE-for-treatment-of-ovarian-cancer-importance-of-kdm6b-and-sirt1-for-er%C3%AE-expression-and-functionality
#5
Giulia Pinton, Stefan Nilsson, Laura Moro
Estrogen receptor (ER) β has growth inhibitory and chemo drug potentiating effect on ovarian cancer cells. We studied the dependence of ERβ function on the presence of KDM6B and SIRT1 in human ovarian cancer cells in vitro. Activation of ERβ with the subtype-selective agonist KB9520 resulted in significant inhibition of human ovarian cancer cell growth. KB9520-activated ERβ had an additive effect on growth inhibition in combination with cisplatin and paclitaxel, respectively. Loss of KDM6B expression had a negative effect on ERβ function as a ligand-dependent inhibitor of ovarian cancer cell growth...
February 9, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29377540/microrna-99a-is-a-novel-regulator-of-kdm6b-mediated-osteogenic-differentiation-of-bmscs
#6
Yin Tang, Lan Zhang, Tianchi Tu, Yijia Li, Dana Murray, Qisheng Tu, Jake Jinkun Chen
Skeletal tissue originates from mesenchymal stem cells (MSCs) with differentiation potential into the osteoblast lineage regulated by essential transcriptional and post-transcriptional mechanisms. Recently, miRNAs and histone modifications have been identified as novel key regulators of osteogenic differentiation of MSCs. Here, we identified miR-99a and its target lysine (K)-specific demethylase 6B (KDM6B) gene as novel modulators of osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Microarray profiling and further validation by quantitative real-time RT-PCR revealed that miR-99a was up-regulated during osteoblastic differentiation of BMSCs, and decreased in differentiated osteoblasts...
January 29, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29355947/corticotropin-releasing-hormone-binding-protein-is-up-regulated-by-brain-derived-neurotrophic-factor-and-is-secreted-in-an-activity-dependent-manner-in-rat-cerebral-cortical-neurons
#7
Naoki Adachi, Shingo Suzuki, Hidetada Matsuoka, Satoko Fushimi, Junichiro Ono, Ken-Ichi Ohta, Yohei Hirai, Takanori Miki, Hisatsugu Koshimizu
A recent study revealed that corticotropin-releasing hormone (CRH) in the cerebral cortex (CTX) plays a regulatory role in emotional behaviors in rodents. Given the functional interaction between brain-derived neurotrophic factor (BDNF) and the CRH-signaling pathway in the hypothalamic-pituitary-adrenal axis, we hypothesized that BDNF may regulate gene expression of CRH and its related molecules in the CTX. Findings of real-time quantitative PCR (RT-qPCR) indicated that stimulation of cultured rat cortical neurons with BDNF led to marked elevations in the mRNA levels of CRH and CRH-binding protein (CRH-BP)...
January 22, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29286640/separation-of-methylated-histone-peptides-via-host-assisted-capillary-electrophoresis
#8
Jiwon Lee, Lizeth Perez, Yang Liu, Hua Wang, Richard J Hooley, Wenwan Zhong
Lysine methylation in protein is one important epigenetic mechanism that regulates diverse biological processes but is challenging to study due to the large variability in methylation levels and sites. Here, we show that supramolecular hosts such as calixarenes and cucurbiturils can be applied in the background electrolyte (BGE) of capillary electrophoresis (CE) for highly effective separation of post-translationally methylated histone peptides. The molecular recognition event causes a shift in the electrophoretic mobility of the peptide, allowing affinity measurement for binding between the synthetic receptor and various methylated lysine species...
February 6, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29220567/structural-basis-of-histone-demethylase-kdm6b-histone-3-lysine-27-specificity
#9
Sarah E Jones, Lars Olsen, Michael Gajhede
KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyze demethylation of di- and trimethylated lysine on histone 3 lysine 27 (H3K27me3/2) and play an important role in repression of developmental genes. Despite identical amino acid sequence in the immediate surroundings of H3K9me3/2 (ARKS), the enzymes do not catalyze demethylation of this general marker of repression. To address this question for KDM6B, we used computational methods to identify H3(17-33)-derived peptides with improved binding affinity that would allow co-crystallization with the catalytic core of human KDM6B (ccKDM6B)...
February 6, 2018: Biochemistry
https://www.readbyqxmd.com/read/29160132/active-h3k27me3-demethylation-by-kdm6b-is-required-for-normal-development-of-bovine-preimplantation-embryos
#10
Nhi Chung, Yanina S Bogliotti, Wei Ding, Marcela Vilarino, Kazuki Takahashi, James L Chitwood, Richard M Schultz, Pablo J Ross
The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3...
2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29108280/trimethylation-of-h3k27-during-human-cerebellar-development-in-relation-to-medulloblastoma
#11
Shahryar E Mir, Michiel Smits, Dennis Biesmans, Machteld Julsing, Marianna Bugiani, Eleonora Aronica, Gertjan J L Kaspers, Jacqueline Cloos, Thomas Würdinger, Esther Hulleman
Medulloblastoma (MB), the most common malignant childhood brain tumor, encompasses a collection of four clinically and molecularly distinct tumor subgroups, i.e. WNT, SHH, Group 3 and Group 4. These tumors are believed to originate from precursor cells during cerebellar development. Although the exact etiology of these brain tumors is not yet known, histone modifications are increasingly recognized as key events during cerebellum development and MB tumorigenesis. Recent studies show that key components involved in post-translational modifications of histone H3 lysine 27 (H3K27) are commonly deregulated in MB...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29082591/the-involvement-of-histone-methylation-in-osteoblastic-differentiation-of-human-periosteum-derived-cells-cultured-in-vitro-under-hypoxic-conditions
#12
Dae-Kwan Yoon, Ji-Sung Park, Gyu-Jin Rho, Hyeon-Jeong Lee, Iel-Yong Sung, Jang-Ho Son, Bong-Wook Park, Young-Hoon Kang, Sung-Hoon Byun, Sun-Chul Hwang, Dong Kyun Woo, Yeong-Cheol Cho, June-Ho Byun
Although oxygen concentrations affect the growth and function of mesenchymal stem cells (MSCs), the impact of hypoxia on osteoblastic differentiation is not understood. Likewise, the effect of hypoxia-induced epigenetic changes on osteoblastic differentiation of MSCs is unknown. The aim of this study was to examine the in vitro hypoxic response of human periosteum-derived cells (hPDCs). Hypoxia resulted in greater proliferation of hPDCs as compared with those cultured in normoxia. Further, hypoxic conditions yielded decreased expression of apoptosis- and senescence-associated genes by hPDCs...
October 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29059104/transfusion-strategies-are-associated-with-epigenetic-changes-following-blunt-trauma
#13
Martin Sillesen, Yongqing Li, Hasan B Alam
INTRODUCTION: Epigenetics has been identified in multiple diseases. The effect of transfusion strategy on epigenetics is unknown. We hypothesized that expression of epigenetic regulating genes would be associated with resuscitation strategy following blunt trauma. METHODS: Retrospective study using the inflammation in host response to injury (glue grant) dataset. Volume transfused over 24 hours of packed red blood cells (PRBC), Fresh Frozen Plasma(FFP), Platelets(PLT) as well as crystalloids was extracted along with leucocyte microarray data of genes with known epigenetic modulating activity from day 1 after injury...
October 20, 2017: Shock
https://www.readbyqxmd.com/read/28962660/local-application-of-igfbp5-protein-enhanced-periodontal-tissue-regeneration-via-increasing-the-migration-cell-proliferation-and-osteo-dentinogenic-differentiation-of-mesenchymal-stem-cells-in-an-inflammatory-niche
#14
Nannan Han, Fengqiu Zhang, Guoqing Li, Xiuli Zhang, Xiao Lin, Haoqing Yang, Lijun Wang, Yangyang Cao, Juan Du, Zhipeng Fan
BACKGROUND: Periodontitis is a widespread infectious disease ultimately resulting in tooth loss. The number of mesenchymal stem cells (MSCs) in patients with periodontitis is decreased, and MSC functions are impaired. Rescuing the impaired function of MSCs in periodontitis is the key for treatment, especially in a manner independent of exogenous MSCs. Our previous study found that overexpressed insulin-like growth factor binding protein 5 (IGFBP5) could promote exogenous MSC-mediated periodontal tissue regeneration...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28854282/endothelial-derived-extracellular-matrix-ameliorate-the-stemness-deprivation-during-ex-vivo-expansion-of-mouse-bone-marrow-derived-mesenchymal-stem-cells
#15
Ming-Kang Lee, Shau-Ping Lin, Wei-Chun HuangFu, Dee-Shiuh Yang, I-Hsuan Liu
Mesenchymal stem cells (MSCs) hold great potential in cell therapies by virtue of the regenerative effects and immunomodulatory properties, but the scarce nature of MSCs makes ex vivo expansion indispensable prior to transplantation purposes. However, potential loss of stemness ensuing culture expansion has hindered the advancements in MSCs-based treatments. In principle, stemness could be preserved by reconstructing the stem cell niche. To test whether the endothelial cells (ECs) participate in the constitution of the stem cell niche for mesenchymal stem cells (MSCs), ECs derivatives including extracellular matrix (ECM) and conditioned medium (CM) prepared from aortic endothelial cells (AECs) and Mile Sven 1 endothelial cell line (MS1) were investigated for the potential to maintain MSCs stemness...
2017: PloS One
https://www.readbyqxmd.com/read/28725537/the-emerging-role-of-histone-demethylases-in-renal-cell-carcinoma
#16
REVIEW
Xiaoqiang Guo, Qiaoxia Zhang
Renal cell carcinoma (RCC), the most common kidney cancer, is responsible for more than 100,000 deaths per year worldwide. The molecular mechanism of RCC is poorly understood. Many studies have indicated that epigenetic changes such as DNA methylation, noncoding RNAs, and histone modifications are central to the pathogenesis of cancer. Histone demethylases (KDMs) play a central role in histone modifications. There is emerging evidence that KDMs such as KDM3A, KDM5C, KDM6A, and KDM6B play important roles in RCC...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28684291/lysine-demethylase-inhibition-protects-pancreatic-%C3%AE-cells-from-apoptosis-and-improves-%C3%AE-cell-function
#17
Marie Balslev Backe, Jan Legaard Andersson, Karl Bacos, Dan Ploug Christensen, Jakob Bondo Hansen, Jerzy Jòzef Dorosz, Michael Gajhede, Tina Dahlby, Madhusudhan Bysani, Line Hyltoft Kristensen, Charlotte Ling, Lars Olsen, Thomas Mandrup-Poulsen
Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress. Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting a possible role in inflammation-induced β-cell destruction...
January 15, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28587848/mir-148a-3p-regulates-adipocyte-and-osteoblast-differentiation-by-targeting-lysine-specific-demethylase-6b
#18
Lijie Tian, Fang Zheng, Zhijia Li, Haixiao Wang, Hairui Yuan, Xin Zhang, Zhongshu Ma, Xiaoxia Li, Xiumei Gao, Baoli Wang
Recent emerging studies of miRNAs in mesenchymal stem cell commitment toward adipocyte and osteoblast provide new insights for the understanding of the molecular basis of adipogenesis and osteogenesis. The current study revealed that miR-148a-3p was altered in primary cultured marrow stromal cells and established stromal ST2 line after adipogenic and/or osteogenic treatment. Supplementing miR-148a-3p activity inhibited cell growth and induced ST2 to differentiate into mature adipocytes. Conversely, inactivation of the endogenous miR-148a-3p suppressed ST2 to fully differentiate...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28502669/biomimetic-tendon-extracellular-matrix-composite-gradient-scaffold-enhances-ligament-to-bone-junction-reconstruction
#19
Huanhuan Liu, Long Yang, Erchen Zhang, Rui Zhang, Dandan Cai, Shouan Zhu, Jisheng Ran, Varitsara Bunpetch, Youzhi Cai, Boon Chin Heng, Yejun Hu, Xuesong Dai, Xiao Chen, Hongwei Ouyang
Management of ligament/tendon-to-bone-junction healing remains a formidable challenge in the field of orthopedic medicine to date, due to deficient vascularity and multi-tissue transitional structure of the junction. Numerous strategies have been employed to improve ligament-bone junction healing, including delivery of stem cells, bioactive factors, and synthetic materials, but these methods are often inadequate at recapitulating the complex structure-function relationships at native tissue interfaces. Here, we developed an easily-fabricated and effective biomimetic composite to promote the regeneration of ligament-bone junction by physically modifying the tendon extracellular matrix (ECM) into a Random-Aligned-Random composite using ultrasound treatment...
May 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28487543/kdm6b-modulates-mapk-pathway-mediating-multiple-myeloma-cell-growth-and-survival
#20
H Ohguchi, T Harada, M Sagawa, S Kikuchi, Y-T Tai, P G Richardson, T Hideshima, K C Anderson
Recent studies have delineated cancer-type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM) cells; and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. Tumor necrosis factor-α or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting that KDM6B is regulated by NF-κB signaling in MM cells...
December 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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