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https://www.readbyqxmd.com/read/29220567/the-structural-basis-of-the-histone-demethylase-kdm6b-histone-3-lysine-27-specificity
#1
Sarah Elizabeth Jones, Lars Olsen, Michael Gajhede
KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyse demethylation of di-/tri-methylated 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 catalyse demethylation of this general marker of repression. In order to address this question for KDM6B we used computational methods to identify H3(17-33) derived peptides with improved binding affinity, that would enable co-crystallization with the catalytic core of human KDM6B (ccKDM6B)...
December 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/29160132/active-h3k27me3-demethylation-by-kdm6b-is-required-for-normal-development-of-bovine-preimplantation-embryos
#2
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...
November 21, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
July 4, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28587848/mir-148a-3p-regulates-adipocyte-and-osteoblast-differentiation-by-targeting-lysine-specific-demethylase-6b
#10
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
#11
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
#12
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...
May 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28469799/histone-h3k14-hypoacetylation-and-h3k27-hypermethylation-along-with-hdac1-up-regulation-and-kdm6b-down-regulation-are-associated-with-active-pulmonary-tuberculosis-disease
#13
Yung-Che Chen, Tung-Ying Chao, Sum-Yee Leung, Chung-Jen Chen, Chao-Chien Wu, Wen-Feng Fang, Yi-Hsi Wang, Huang-Chih Chang, Ting-Ya Wang, Yong-Yong Lin, Yi-Xin Zheng, Meng-Chih Lin, Chang-Chun Hsiao
The aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in active pulmonary tuberculosis (TB) disease. Global histone H3K27me3, H3K27me2, H3K9me3, H3K9Ac, and H3K14Ac expressions, and their modifying enzyme expressions, including KDM1A, KDM6B, EZH2, HDAC1, and HDAC2, were assessed in blood leukocytes from 81 patients with active pulmonary TB disease and 44 matched healthy subjects (HS). TLR2, TNF-α, IFN-γ, and IL12B-specific histone enrichment of peripheral blood mononuclear cells was measured by chromatin immunoprecipitation method...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28455435/cd40l-dependent-pathway-is-active-at-various-stages-of-rheumatoid-arthritis-disease-progression
#14
Yanxia Guo, Alice M Walsh, Ursula Fearon, Malcolm D Smith, Mihir D Wechalekar, Xuefeng Yin, Suzanne Cole, Carl Orr, Trudy McGarry, Mary Canavan, Stephan Kelly, Tai-An Lin, Xuejun Liu, Susanna M Proudman, Douglas J Veale, Costantino Pitzalis, Sunil Nagpal
The inflammatory CD40-CD40L pathway is implicated in various autoimmune diseases, but the activity status of this pathway in various stages of rheumatoid arthritis (RA) progression is unknown. In this study, we used gene signatures of CD40L stimulation derived from human immature dendritic cells and naive B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab-positive arthralgia, undifferentiated arthritis (UA), early RA, and established RA cohorts in comparison with healthy donors...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28413430/next-generation-sequencing-of-non-small-cell-lung-cancer-using-a-customized-targeted-sequencing-panel-emphasis-on-small-biopsy-and-cytology
#15
David M DiBardino, David W Rawson, Anjali Saqi, Jonas J Heymann, Carlos A Pagan, William A Bulman
BACKGROUND: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. MATERIALS AND METHODS: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015...
2017: CytoJournal
https://www.readbyqxmd.com/read/28384648/regulation-of-the-jmjd3-kdm6b-histone-demethylase-in-glioblastoma-stem-cells-by-stat3
#16
Maureen M Sherry-Lynes, Sejuti Sengupta, Shreya Kulkarni, Brent H Cochran
The growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect...
2017: PloS One
https://www.readbyqxmd.com/read/28372944/histone-demethylases-kdm6ba-and-kdm6bb-redundantly-promote-cardiomyocyte-proliferation-during-zebrafish-heart-ventricle-maturation
#17
Alexander A Akerberg, Astra Henner, Scott Stewart, Kryn Stankunas
Trimethylation of lysine 27 on histone 3 (H3K27me3) by the Polycomb repressive complex 2 (PRC2) contributes to localized and inherited transcriptional repression. Kdm6b (Jmjd3) is a H3K27me3 demethylase that can relieve repression-associated H3K27me3 marks, thereby supporting activation of previously silenced genes. Kdm6b is proposed to contribute to early developmental cell fate specification, cardiovascular differentiation, and/or later steps of organogenesis, including endochondral bone formation and lung development...
June 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28322580/macrophage-kdm6b-controls-the-pro-fibrotic-transcriptome-signature-of-foam-cells
#18
Annette E Neele, Koen Hm Prange, Marten A Hoeksema, Saskia van der Velden, Tina Lucas, Stefanie Dimmeler, Esther Lutgens, Jan Van den Bossche, Menno Pj de Winther
AIM: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. MATERIALS & METHODS: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. RESULTS: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells...
April 2017: Epigenomics
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#19
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
July 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28228757/regulation-of-epigenetic-modifiers-including-kdm6b-by-interferon-%C3%AE-and-interleukin-4-in-human-macrophages
#20
Gökçe Yıldırım-Buharalıoğlu, Mark Bond, Graciela B Sala-Newby, Charles C T Hindmarch, Andrew C Newby
BACKGROUND: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood. METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction...
2017: Frontiers in Immunology
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