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https://www.readbyqxmd.com/read/27789700/reciprocal-regulation-of-chromatin-state-and-architecture-by-hotairm1-contributes-to-temporal-collinear-hoxa-gene-activation
#1
Xue Q D Wang, Josée Dostie
Thousands of long non-coding RNAs (lncRNAs) have been identified in mammals, many of which represent important regulators of gene expression. However, the mechanisms used by lncRNAs to control transcription remain largely uncharacterized. Here, we report on HOTAIRM1, a promising lncRNA biomarker in leukemia and solid tumors. We find that HOTAIRM1 contributes to three-dimensional chromatin organization changes required for the temporal collinear activation of HOXA genes. We show that distinct HOTAIRM1 variants preferentially associate with either UTX/MLL or PRC2 complexes to modulate the levels of activating and silencing marks at the bivalent domain...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27786258/surgical-technique-for-allogeneic-uterus-transplantation-in-macaques
#2
Hideaki Obara, Iori Kisu, Yojiro Kato, Yohei Yamada, Kentaro Matsubara, Katsura Emoto, Masataka Adachi, Yusuke Matoba, Kiyoko Umene, Yuya Nogami, Kouji Banno, Hideaki Tsuchiya, Iori Itagaki, Ikuo Kawamoto, Takahiro Nakagawa, Hirohito Ishigaki, Yasushi Itoh, Kazumasa Ogasawara, Yoko Saiki, Shin-Ichi Sato, Kenshi Nakagawa, Takashi Shiina, Daisuke Aoki, Yuko Kitagawa
No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27722168/role-of-histone-demethylases-in-cardiomyocytes-induced-to-hypertrophy
#3
Wendy Rosales, Juan Carulla, Jeison García, Diana Vargas, Fernando Lizcano
Epigenetic changes induced by histone demethylases play an important role in differentiation and pathological changes in cardiac cells. However, the role of the jumonji family of demethylases in the development of cardiac hypertrophy remains elusive. In this study, the presence of different histone demethylases in cardiac cells was evaluated after hypertrophy was induced with neurohormones. A cell line from rat cardiomyocytes was used as a biological model. The phenotypic profiles of the cells, as well as the expression of histone demethylases, were studied through immunofluorescence, transient transfection, western blot, and qRT-PCR analysis after inducing hypertrophy by angiotensin II and endothelin-1...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27671333/utx-1-regulates-tat-induced-hiv-1-transactivation-via-changing-the-methylated-status-of-histone-h3
#4
Hong-Sheng Zhang, Guang-Yuan Du, Yang Liu, Zhong-Guo Zhang, Zhen Zhou, Hu Li, Ke-Qing Dai, Xiao-Ying Yu, Xiao-Meng Gou
Epigenetic modifications are thought to be important for gene expression changes during HIV-1 transcription and replication. The removal of histone H3 lysine27 (H3K27) trimethylation mark by UTX-1 is important for the robust induction of many specific genes during Tat-mediated HIV-1 transactvation. We found that UTX-1 enzymatic activity is needed for Tat to remove a repressive mark H3K27me3 in the HIV-1 long terminal repeat (LTR). UTX-1 converted the chromatin structure to a more transcriptionally active state by up-regulation of H3K4 methylation and down-regulation of H3K27 methylation on the specific regions of HIV-1 LTR...
September 23, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27638352/mll3-mll4-compass-family-on-epigenetic-regulation-of-enhancer-function-and-cancer
#5
Christie C Sze, Ali Shilatifard
During development, precise spatiotemporal patterns of gene expression are coordinately controlled by cis-regulatory modules known as enhancers. Their crucial role in development helped spur numerous studies aiming to elucidate the functional properties of enhancers within their physiological and disease contexts. In recent years, the role of enhancer malfunction in tissue-specific tumorigenesis is increasingly investigated. Here, we direct our focus to two primary players in enhancer regulation and their role in cancer pathogenesis: MLL3 and MLL4, members of the COMPASS family of histone H3 lysine 4 (H3K4) methyltransferases, and their complex-specific subunit UTX, a histone H3 lysine 27 (H3K27) demethylase...
September 16, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27602485/increasing-notch-signaling-antagonizes-prc2-mediated-silencing-to-promote-reprograming-of-germ-cells-into-neurons
#6
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/27578004/histone-h3k27-trimethylation-modulates-5-fluorouracil-resistance-by-inhibiting-pu-1-binding-to-the-dpyd-promoter
#7
Rentian Wu, Qian Nie, Erin E Tapper, Calvin R Jerde, Garrett S Dunlap, Shikshya Shrestha, Tarig A Elraiyah, Steven M Offer, Robert B Diasio
The antimetabolite 5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs. Dihydropyrimidine dehydrogenase (DPD) is a major determinant of 5-FU response and toxicity. Although DPYD variants may affect 5-FU metabolism, they do not completely explain the reported variability in DPD function or the resultant differences in treatment response. Here, we report that H3K27 trimethylation (H3K27me3) at the DPYD promoter regulated by Ezh2 and UTX suppresses DPYD expression by inhibiting transcription factor PU...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27552172/uterus-transplantation-in-france-for-which-patients
#8
S Huet, A Tardieu, M Filloux, M Essig, N Pichon, J F Therme, P Piver, Y Aubard, J M Ayoubi, O Garbin, P Collinet, A Agostini, V Lavoue, A Piccardo, T Gauthier
OBJECTIVE: Uterine infertility (UI), which can be caused by a variety of congenital or acquired factors, affects several thousand women in Europe. Uterus transplantation (UTx), at the current stage of research, offers hope for these women to be both the biological mother and the carrier of their child. However, the indications of UTx still need to be defined. The main aim of the study was to describe the different etiologies of UI and other data as marital and parental status from women requesting UTx who contacted us in the framework of a UTx clinical trial...
October 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27533081/target-sequencing-and-crispr-cas-editing-reveal-simultaneous-loss-of-utx-and-uty-in-urothelial-bladder-cancer
#9
Jinwoo Ahn, Kwang Hyun Kim, Sanghui Park, Young-Ho Ahn, Ha Young Kim, Hana Yoon, Ji Hyun Lee, Duhee Bang, Dong Hyeon Lee
UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27528513/the-histone-demethylase-inhibitor-gsk-j4-limits-inflammation-through-the-induction-of-a-tolerogenic-phenotype-on-dcs
#10
Cristian Doñas, Macarena Carrasco, Macarena Fritz, Carolina Prado, Gabriela Tejón, Francisco Osorio-Barrios, Valeria Manríquez, Paz Reyes, Rodrigo Pacheco, María Rosa Bono, Alejandra Loyola, Mario Rosemblatt
As it has been established that demethylation of lysine 27 of histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize that inhibition of JMJD3 may attenuate autoimmune disorders. We found that in vivo administration of GSK-J4, a selective inhibitor of JMJD3 and UTX, ameliorates the severity of experimental autoimmune encephalomyelitis (EAE). In vitro experiments revealed that the anti-inflammatory effect of GSK-J4 was exerted through an effect on dendritic cells (DCs), promoting a tolerogenic profile characterized by reduced expression of costimulatory molecules CD80/CD86, an increased expression of tolerogenic molecules CD103 and TGF-β1, and reduced secretion of proinflammatory cytokines IL-6, IFN-γ, and TNF...
August 12, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27458035/the-roles-of-histone-demethylase-utx-and-jmjd3-kdm6b-in-cancers-current-progress-and-future-perspectives
#11
Zhan Gang Xiao, Jing Shen, Lin Zhang, Long Fei Li, Ming Xing Li, Wei Hu, Zhi Jie Li, Chi Hin Cho
Aberrant epigenetic reprogramming occurs frequently in the development of tumors. Histone H3 lysine 27 trimethylation (H3K27me3) exerts a repressive epigenetic mark on a large number of genes. UTX and JMJD3 are the only two histone demethylases which activate gene expression via demethylating H3K27me3 to H3K27me2 or H3K27me1. Current studies show that dysregulation of these two proteins are heavily linked to oncogenesis in various tissue types. Accumulating evidence suggested that there is remarkable therapeutic potential of targeting JMJD3 or UTX in different types of cancer...
July 24, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27422088/structural-insight-into-protein-binding-of-boron-tracedrug-utx-97-revealed-by-the-co-crystal-structure-with-lysozyme-at-1-26-%C3%A3-resolution
#12
Yukio Morimoto, Hideko Nagasawa, Yoshihiro Uto, Toshiyuki Chatake, Hitoshi Hori
Boron neutron capture therapy (BNCT) is one of the numbers of radiotherapies for treatment of certain cancers. The ability of low-dose irradiation with neutrons or radioactive beams to provide an acceptable quality of life is an objective which has not yet been achieved; therefore it will be necessary to increase the efficiency of the neutron capture reaction by lower dose irradiation and by achieving higher drug concentrations in living cells. Drug selectivity in targeting the affected cellular compartment is most important...
August 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27388528/h3k27me3-demethylases-regulate-in-vitro-chondrogenesis-and-chondrocyte-activity-in-osteoarthritis
#13
Clarence Yapp, Andrew J Carr, Andrew Price, Udo Oppermann, Sarah J B Snelling
BACKGROUND: Epigenetic changes (i.e., chromatin modifications) occur during chondrogenesis and in osteoarthritis (OA). We investigated the effect of H3K27me3 demethylase inhibition on chondrogenesis and assessed its utility in cartilage tissue engineering and in understanding cartilage destruction in OA. METHODS: We used a high-content screen to assess the effect of epigenetic modifying compounds on collagen output during chondrogenesis of monolayer human mesenchymal stem cells (MSCs)...
2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27384759/the-maternal-effect-genes-utx-and-jmjd3-play-contrasting-roles-in-mus-musculus-preimplantation-embryo-development
#14
Lei Yang, Li-Shuang Song, Xue-Fei Liu, Qing Xia, Li-Ge Bai, Li Gao, Guang-Qi Gao, Yu Wang, Zhu-Ying Wei, Chun-Ling Bai, Guang-Peng Li
During the process of embryonic development in mammals, epigenetic modifications must be erased and reconstructed. In particular, the trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcriptional repression and contributes to the maintenance of the pluripotent embryos. In this study, we determined that the global levels of the H3K27me3 marker were elevated in MII oocyte chromatin and decrease to minimal levels at the 8-cell and morula stages. When the blastocyst hatched, H3K27me3 was re-established in the inner cell mass...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27367247/increased-expression-of-the-histone-h3-lysine-4-methyltransferase-mll4-and-the-histone-h3-lysine-27-demethylase-utx-prolonging-the-overall-survival-of-patients-with-glioblastoma-and-a-methylated-mgmt-promoter
#15
Jinho Kim, Sung-Hun Lee, Ji Hwan Jang, Mee-Seon Kim, Eun Hee Lee, Young Zoon Kim
OBJECTIVE The purpose of the present study was to investigate the epigenetic and prognostic roles of an H3K4 methyltransferase (mixed lineage leukemia 4 [MLL4]) and H3K27 demethylase (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome [UTX]) in progression-free survival (PFS) and overall survival (OS) of patients with glioblastoma (GBM) who were treated with radiotherapy, chemotherapy, or both after resection. In addition, the authors examined methylation at the promoter of the O-6-methylguanine-DNA methyltransferase (MGMT) gene and other prognostic factors predicting length of PFS and OS in these patients...
July 1, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27339988/identification-of-an-nkx3-1-g9a-uty-transcriptional-regulatory-network-that-controls-prostate-differentiation
#16
Aditya Dutta, Clémentine Le Magnen, Antonina Mitrofanova, Xuesong Ouyang, Andrea Califano, Cory Abate-Shen
The NKX3.1 homeobox gene plays essential roles in prostate differentiation and prostate cancer. We show that loss of function of Nkx3.1 in mouse prostate results in down-regulation of genes that are essential for prostate differentiation, as well as up-regulation of genes that are not normally expressed in prostate. Conversely, gain of function of Nkx3.1 in an otherwise fully differentiated nonprostatic mouse epithelium (seminal vesicle) is sufficient for respecification to prostate in renal grafts in vivo...
June 24, 2016: Science
https://www.readbyqxmd.com/read/27235425/the-spectrum-and-clinical-impact-of-epigenetic-modifier-mutations-in-myeloma
#17
Charlotte Pawlyn, Martin F Kaiser, Christoph Heuck, Lorenzo Melchor, Christopher P Wardell, Alex Murison, Shweta S Chavan, David C Johnson, Dil B Begum, Nasrin M Dahir, Paula Z Proszek, David A Cairns, Eileen M Boyle, John R Jones, Gordon Cook, Mark T Drayson, Roger G Owen, Walter M Gregory, Graham H Jackson, Bart Barlogie, Faith E Davies, Brian A Walker, Gareth J Morgan
PURPOSE: Epigenetic dysregulation is known to be an important contributor to myeloma pathogenesis but, unlike other B-cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been reported previously. We sought to address this using the results from whole-exome sequencing in the context of a large prospective clinical trial of newly diagnosed patients and targeted sequencing in a cohort of previously treated patients for comparison. EXPERIMENTAL DESIGN: Whole-exome sequencing analysis of 463 presenting myeloma cases entered in the UK NCRI Myeloma XI study and targeted sequencing analysis of 156 previously treated cases from the University of Arkansas for Medical Sciences (Little Rock, AR)...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27228653/-product-of-the-bmi1-a-key-component-of-polycomb-positively-regulates-adipocyte-differentiation-of-mouse-mesenchymal-stem-cells
#18
N S Petrov, N A Vereschagina, E N Sushilova, A V Kropotov, N F Miheeva, B V Popov
Bmil is a key component of Polycomb (PcG), which in mammals controls the basic functions of mammalian somatic stem cells (SSC) such as self-renewal and differentiation. Bmi1 supports SSC via transcriptional suppression of genes associated with cell cycle and differentiation. The most studied target genes of Bmi1 are the genes of Ink4 locus, CdkI p16(Ink4a) and p1(Arf), suppression of which due to activating mutations of the BMI1 results in formation of cancer stem cells (CSC) and carcinomas in various tissues...
2016: Tsitologiia
https://www.readbyqxmd.com/read/27224921/screen-identified-selective-inhibitor-of-lysine-demethylase-5a-blocks-cancer-cell-growth-and-drug-resistance
#19
Molly Gale, Joyce Sayegh, Jian Cao, Michael Norcia, Peter Gareiss, Denton Hoyer, Jane S Merkel, Qin Yan
Lysine demethylase 5A (KDM5A/RBP2/JARID1A) is a histone lysine demethylase that is overexpressed in several human cancers including lung, gastric, breast and liver cancers. It plays key roles in important cancer processes including tumorigenesis, metastasis, and drug tolerance, making it a potential cancer therapeutic target. Chemical tools to analyze KDM5A demethylase activity are extremely limited as available inhibitors are not specific for KDM5A. Here, we characterized KDM5A using a homogeneous luminescence-based assay and conducted a screen of about 9,000 small molecules for inhibitors...
May 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27203855/survey-of-attitudes-toward-uterus-transplantation-among-japanese-women-of-reproductive-age-a-cross-sectional-study
#20
Iori Kisu, Kouji Banno, Etsuko Soeda, Yuki Kurihara, Miho Okushima, Ami Yamaguchi, Eriko Nakagawa, Kiyoko Umene, Daisuke Aoki
OBJECTIVE: Uterus transplantation (UTx) is a potential option for women with uterine factor infertility to have a child, but there has been no large-scale survey of the views on UTx in women of reproductive age in Japan. The present study was aimed to clarify the views of Japanese women of reproductive age on UTx for uterine factor infertility. METHODS: A questionnaire on UTx was conducted by an Internet research company in December 2014 as a cross-sectional study in 3,892 randomly chosen women aged 25 to 39 years old...
2016: PloS One
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