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https://www.readbyqxmd.com/read/27904015/deletion-of-conserved-sequences-in-ig-dmr-at-dlk1-gtl2-locus-suggests-their-involvement-in-expression-of-paternally-expressed-genes-in-mice
#1
Takeshi Saito, Satoshi Hara, Moe Tamano, Hiroshi Asahara, Shuji Takada
Expression regulation of the Dlk1-Dio3 imprinted domain by the intergenic differentially methylated region (IG-DMR) is essential for normal embryonic development in mammals. In this study, we investigated conserved IG-DMR genomic sequences in eutherians to elucidate their role in genomic imprinting of the Dlk1-Dio3 domain. Using a comparative genomics approach, we identified three highly conserved sequences in IG-DMR. To elucidate the functions of these sequences in vivo, we generated mutant mice lacking each of the identified highly conserved sequences using the CRISPR/Cas9 system...
December 1, 2016: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/27832204/expression-of-the-lncrna-maternally-expressed-gene-3-meg3-contributes-to-the-control-of-lung-cancer-cell-proliferation-by-the-rb-pathway
#2
Traci L Kruer, Susan M Dougherty, Lindsey Reynolds, Elizabeth Long, Tanya de Silva, William W Lockwood, Brian F Clem
Maternally expressed gene 3 (MEG3, mouse homolog Gtl2) encodes a long noncoding RNA (lncRNA) that is expressed in many normal tissues, but is suppressed in various cancer cell lines and tumors, suggesting it plays a functional role as a tumor suppressor. Hypermethylation has been shown to contribute to this loss of expression. We now demonstrate that MEG3 expression is regulated by the retinoblastoma protein (Rb) pathway and correlates with a change in cell proliferation. Microarray analysis of mouse embryonic fibroblasts (MEFs) isolated from mice with genetic deletion of all three Rb family members (TKO) revealed a significant silencing of Gtl2/MEG3 expression compared to WT MEFs, and re-expression of Gtl2/MEG3 caused decrease in cell proliferation and increased apoptosis...
2016: PloS One
https://www.readbyqxmd.com/read/27777636/maternal-vitamin-d-depletion-alters-dna-methylation-at-imprinted-loci-in-multiple-generations
#3
Jing Xue, Sarah A Schoenrock, William Valdar, Lisa M Tarantino, Folami Y Ideraabdullah
BACKGROUND: Environmental perturbation of epigenetic mechanisms is linked to a growing number of diseases. Characterizing the role environmental factors play in modifying the epigenome is important for disease etiology. Vitamin D is an essential nutrient affecting brain, bone, heart, immune and reproductive health. Vitamin D insufficiency is a global issue, and the role in maternal and child health remains under investigation. METHODS: We used Collaborative Cross (CC) inbred mice to characterize the effect of maternal vitamin D depletion on offspring phenotypic and epigenetic outcomes at imprinted domains (H19/Igf2, Snrpn, Dlk1/Gtl2, and Grb10) in the soma (liver) and germline (sperm)...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27580759/parentally-imprinted-genes-regulate-hematopoiesis-new-evidence-from-the-dlk1-gtl2-locus
#4
EDITORIAL
Gabriela Schneider, Zachariah Payne Sellers, Mariusz Z Ratajczak
No abstract text is available yet for this article.
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27531747/the-influence-of-polyploidy-and-genome-composition-on-genomic-imprinting-in-mice
#5
Wataru Yamazaki, Tomoko Amano, Hanako Bai, Masashi Takahashi, Manabu Kawahara
Genomic imprinting is an epigenetic mechanism that switches the expression of imprinted genes involved in normal embryonic growth and development in a parent-of-origin-specific manner. Changes in DNA methylation statuses from polyploidization are a well characterized epigenetic modification in plants. However, how changes in ploidy affect both imprinted gene expression and methylation status in mammals remains unclear. To address this, we used quantitative real time PCR to analyze expression levels of imprinted genes in mouse tetraploid fetuses...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27486249/erasure-of-dna-methylation-genomic-imprints-and-epimutations-in-a-primordial-germ-cell-model-derived-from-mouse-pluripotent-stem-cells
#6
Norikatsu Miyoshi, Jente M Stel, Keiko Shioda, Na Qu, Junko Odahima, Shino Mitsunaga, Xiangfan Zhang, Makoto Nagano, Konrad Hochedlinger, Kurt J Isselbacher, Toshi Shioda
The genome-wide depletion of 5-methylcytosines (5meCs) caused by passive dilution through DNA synthesis without daughter strand methylation and active enzymatic processes resulting in replacement of 5meCs with unmethylated cytosines is a hallmark of primordial germ cells (PGCs). Although recent studies have shown that in vitro differentiation of pluripotent stem cells (PSCs) to PGC-like cells (PGCLCs) mimics the in vivo differentiation of epiblast cells to PGCs, how DNA methylation status of PGCLCs resembles the dynamics of 5meC erasure in embryonic PGCs remains controversial...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27369467/evaluation-of-dna-methylation-at-imprinted-dmrs-in-the-spermatozoa-of-oligozoospermic-men-in-association-with-mthfr-c677t-genotype
#7
K Louie, A Minor, R Ng, K Poon, V Chow, S Ma
Altered DNA methylation has been previously identified in the spermatozoa of infertile men; however, the origins of these errors are poorly understood. DNA methylation is an epigenetic modification which is thought to play a fundamental role in male germline development. DNA methylation reactions rely on the cellular availability of methyl donors, which are primarily products of folate metabolism, where a key enzyme is methylenetetrahydrofolate reductase (MTHFR). The MTHFR C677T single nucleotide polymorphism (SNP) reduces enzyme activity and may potentially alter DNA methylation processes during germline development...
September 2016: Andrology
https://www.readbyqxmd.com/read/27138065/generation-and-application-of-mammalian-haploid-embryonic-stem-cells
#8
M Bai, Y Wu, J Li
Haploid cells contain one set of chromosomes and are amenable for genetic analyses. In mammals, haploidy exists only in gametes. An intriguing question is whether haploid cells can be derived from gametes. Recently, by application of haploid cell enrichment using fluorescence-activated cell sorting, stable haploid embryonic stem cells (haESCs) have been successfully derived from oocyte-derived parthenogenetic and sperm-derived androgenetic embryos from several species. Whilst both parthenogenetic and androgenetic (AG)-haESCs enable whole-genome genetic screening at the cellular level, such as screening of drug resistance or disease-related genes, AG-haESCs, after intracytoplasmic injection into oocytes, can also be used to produce alive semi-cloned mice...
September 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/26999812/mir-410-and-mir-495-are-dynamically-regulated-in-diverse-cardiomyopathies-and-their-inhibition-attenuates-pathological-hypertrophy
#9
Amanda L Clark, Sonomi Maruyama, Soichi Sano, Anthony Accorsi, Mahasweta Girgenrath, Kenneth Walsh, Francisco J Naya
Noncoding RNAs have emerged as important modulators in cardiac development and pathological remodeling. Recently, we demonstrated that regulation of the Gtl2-Dio3 noncoding RNA locus is dependent on the MEF2 transcription factor in cardiac muscle, and that two of its encoded miRNAs, miR-410 and miR-495, induce robust cardiomyocyte proliferation. Given the possibility of manipulating the expression of these miRNAs to repair the damaged heart by stimulating cardiomyocyte proliferation, it is important to determine whether the Gtl2-Dio3 noncoding RNAs are regulated in cardiac disease and whether they function downstream of pathological cardiac stress signaling...
2016: PloS One
https://www.readbyqxmd.com/read/26991405/embryos-aggregation-improves-development-and-imprinting-gene-expression-in-mouse-parthenogenesis
#10
Guang-Yu Bai, Si-Hang Song, Zhen-Dong Wang, Zhi-Yan Shan, Rui-Zhen Sun, Chun-Jia Liu, Yan-Shuang Wu, Tong Li, Lei Lei
Mouse parthenogenetic embryonic stem cells (PgESCs) could be applied to study imprinting genes and are used in cell therapy. Our previous study found that stem cells established by aggregation of two parthenogenetic embryos at 8-cell stage (named as a2 PgESCs) had a higher efficiency than that of PgESCs, and the paternal expressed imprinting genes were observably upregulated. Therefore, we propose that increasing the number of parthenogenetic embryos in aggregation may improve the development of parthenogenetic mouse and imprinting gene expression of PgESCs...
April 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/26974671/abnormal-hypermethylation-at-imprinting-control-regions-in-patients-with-s-adenosylhomocysteine-hydrolase-ahcy-deficiency
#11
MULTICENTER STUDY
Antje Motzek, Jelena Knežević, Olivier J Switzeny, Alexis Cooper, Ivo Barić, Robert Beluzić, Kevin A Strauss, Erik G Puffenberger, S Harvey Mudd, Oliver Vugrek, Ulrich Zechner
S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare autosomal recessive disorder in methionine metabolism caused by mutations in the AHCY gene. Main characteristics are psychomotor delay including delayed myelination and myopathy (hypotonia, absent tendon reflexes etc.) from birth, mostly associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome wide DNA methylation. The prime function of AHCY is to hydrolyse and efficiently remove S-adenosylhomocysteine, the by-product of transmethylation reactions and one of the most potent methyltransferase inhibitors...
2016: PloS One
https://www.readbyqxmd.com/read/26938548/effects-of-gold-nanorods-on-imprinted-genes-expression-in-tm-4-sertoli-cells
#12
Beilei Yuan, Hao Gu, Bo Xu, Qiuqin Tang, Wei Wu, Xiaoli Ji, Yankai Xia, Lingqing Hu, Daozhen Chen, Xinru Wang
Gold nanorods (GNRs) are among the most commonly used nanomaterials. However, thus far, little is known about their harmful effects on male reproduction. Studies from our laboratory have demonstrated that GNRs could decrease glycine synthesis, membrane permeability, mitochondrial membrane potential and disrupt blood-testis barrier factors in TM-4 Sertoli cells. Imprinted genes play important roles in male reproduction and have been identified as susceptible loci to environmental insults by chemicals because they are functionally haploid...
March 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/26849297/mom-knows-best-imprinted-control-of-hematopoietic-stem-cell-quiescence
#13
COMMENT
Juana Serrano-Lopez, Jose A Cancelas
The mechanisms by which imprinted loci control activity of hematopoietic stem cells (HSCs) are not known. In this issue of Cell Stem Cell, Qian et al. (2016) demonstrate that non-coding RNAs expressed by the maternal-imprinted locus Dlk1-Gtl2 maintain HSC self-renewal through the inhibition of PI3K-mTOR signaling, mitochondrial biogenesis, and metabolic activity.
February 4, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/26729373/improved-transcription-and-translation-with-l-leucine-stimulation-of-mtorc1-in-roberts-syndrome
#14
Baoshan Xu, Madelaine Gogol, Karin Gaudenz, Jennifer L Gerton
BACKGROUND: Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2. We previously reported that mTORC1 signaling was depressed and overall translation was reduced in RBS cells and zebrafish models for RBS. Treatment of RBS cells and zebrafish RBS models with L-leucine partially rescued mTOR function and protein synthesis, correlating with increased cell division and improved development. RESULTS: In this study, we use RBS cells to model mTORC1 repression and analyze transcription and translation with ribosome profiling to determine gene-level effects of L-leucine...
2016: BMC Genomics
https://www.readbyqxmd.com/read/26627594/the-dlk1-gtl2-locus-preserves-lt-hsc-function-by-inhibiting-the-pi3k-mtor-pathway-to-restrict-mitochondrial-metabolism
#15
Pengxu Qian, Xi C He, Ariel Paulson, Zhenrui Li, Fang Tao, John M Perry, Fengli Guo, Meng Zhao, Lei Zhi, Aparna Venkatraman, Jeffrey S Haug, Tari Parmely, Hua Li, Rick T Dobrowsky, Wen-Xing Ding, Tomohiro Kono, Anne C Ferguson-Smith, Linheng Li
The mammalian imprinted Dlk1-Gtl2 locus produces multiple non-coding RNAs (ncRNAs) from the maternally inherited allele, including the largest miRNA cluster in the mammalian genome. This locus has characterized functions in some types of stem cell, but its role in hematopoietic stem cells (HSCs) is unknown. Here, we show that the Dlk1-Gtl2 locus plays a critical role in preserving long-term repopulating HSCs (LT-HSCs). Through transcriptome profiling in 17 hematopoietic cell types, we found that ncRNAs expressed from the Dlk1-Gtl2 locus are predominantly enriched in fetal liver HSCs and the adult LT-HSC population and sustain long-term HSC functionality...
February 4, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/26527006/trim28-controls-genomic-imprinting-through-distinct-mechanisms-during-and-after-early-genome-wide-reprogramming
#16
Katherine A Alexander, Xu Wang, Maho Shibata, Andrew G Clark, María J García-García
Genomic imprinting depends on the establishment and maintenance of DNA methylation at imprinting control regions. However, the mechanisms by which these heritable marks influence allele-specific expression are not fully understood. By analyzing maternal, zygotic, maternal-zygotic, and conditional Trim28 mutants, we found that the transcription factor TRIM28 controls genomic imprinting through distinct mechanisms at different developmental stages. During early genome-wide reprogramming, both maternal and zygotic TRIM28 are required for the maintenance of methylation at germline imprints...
November 10, 2015: Cell Reports
https://www.readbyqxmd.com/read/26307085/high-dose-folic-acid-supplementation-alters-the-human-sperm-methylome-and-is-influenced-by-the-mthfr-c677t-polymorphism
#17
Mahmoud Aarabi, Maria C San Gabriel, Donovan Chan, Nathalie A Behan, Maxime Caron, Tomi Pastinen, Guillaume Bourque, Amanda J MacFarlane, Armand Zini, Jacquetta Trasler
Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility...
November 15, 2015: Human Molecular Genetics
https://www.readbyqxmd.com/read/26302774/downregulation-of-il6-targeted-mir-376b-may-contribute-to-a-positive-il6-feedback-loop-during-early-liver-regeneration-in-mice
#18
Shan Lu, Heng Jiao, Juan Xu, Yongxia Zheng, Yimin Sun, Huan Chen
BACKGROUND/AIMS: MicroRNAs (miRNAs) are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration. METHODS: MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed...
2015: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26299972/prc2-is-required-to-maintain-expression-of-the-maternal-gtl2-rian-mirg-locus-by-preventing-de-novo-dna-methylation-in-mouse-embryonic-stem-cells
#19
Partha Pratim Das, David A Hendrix, Effie Apostolou, Alice H Buchner, Matthew C Canver, Semir Beyaz, Damir Ljuboja, Rachael Kuintzle, Woojin Kim, Rahul Karnik, Zhen Shao, Huafeng Xie, Jian Xu, Alejandro De Los Angeles, Yingying Zhang, Junho Choe, Don Leong Jia Jun, Xiaohua Shen, Richard I Gregory, George Q Daley, Alexander Meissner, Manolis Kellis, Konrad Hochedlinger, Jonghwan Kim, Stuart H Orkin
Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus...
September 1, 2015: Cell Reports
https://www.readbyqxmd.com/read/26240138/micrornas-in-the-myocyte-enhancer-factor-2-mef2-regulated-gtl2-dio3-noncoding-rna-locus-promote-cardiomyocyte-proliferation-by-targeting-the-transcriptional-coactivator-cited2
#20
Amanda L Clark, Francisco J Naya
Understanding cell cycle regulation in postmitotic cardiomyocytes may lead to new therapeutic approaches to regenerate damaged cardiac tissue. We have demonstrated previously that microRNAs encoded by the Gtl2-Dio3 noncoding RNA locus function downstream of the MEF2A transcription factor in skeletal muscle regeneration. We have also reported expression of these miRNAs in the heart. Here we investigated the role of two Gtl2-Dio3 miRNAs, miR-410 and miR-495, in cardiac muscle. Overexpression of miR-410 and miR-495 robustly stimulated cardiomyocyte DNA synthesis and proliferation...
September 18, 2015: Journal of Biological Chemistry
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