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https://www.readbyqxmd.com/read/29628311/a-family-of-vertebrate-specific-polycombs-encoded-by-the-lcor-lcorl-genes-balance-prc2-subtype-activities
#1
Eric Conway, Emilia Jerman, Evan Healy, Shinsuke Ito, Daniel Holoch, Giorgio Oliviero, Orla Deevy, Eleanor Glancy, Darren J Fitzpatrick, Marlena Mucha, Ariane Watson, Alan M Rice, Paul Chammas, Christine Huang, Indigo Pratt-Kelly, Yoko Koseki, Manabu Nakayama, Tomoyuki Ishikura, Gundula Streubel, Kieran Wynne, Karsten Hokamp, Aoife McLysaght, Claudio Ciferri, Luciano Di Croce, Gerard Cagney, Raphaël Margueron, Haruhiko Koseki, Adrian P Bracken
The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2), little is known about their differential functions. Here, we report the discovery of a family of vertebrate-specific PRC2.1 proteins, "PRC2 associated LCOR isoform 1" (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively...
April 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29563122/epigenetic-programming-of-t-cells-impacts-immune-reconstitution-in-hematopoietic-stem-cell-transplant-recipients
#2
Kristine Hardy, Corey Smith, Wen Juan Tu, Robert McCuaig, Archana Panikkar, Vijayendra Dasari, Fan Wu, Siok-Keen Tey, Geoffrey R Hill, Rajiv Khanna, Sudha Rao
Immune reconstitution following hematopoietic stem cell transplantation (HSCT) is critical in preventing harmful sequelae in recipients with cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying immune reconstitution kinetics, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8+ T cells from HCST recipients with different immune reconstitution efficiencies. CMV-specific T cells from HSCT recipients with stable antiviral immunity expressed higher levels of interferon/defense response and cell cycle genes in an interconnected network involving PI3KCG , STAT5B , NFAT , RBPJ , and lower HDAC6 , increasing chromatin accessibility at the enhancer regions of immune and T-cell receptor signaling pathway genes...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29546425/redox-sensitive-transcription-factor-nrf2-enhances-trophoblast-differentiation-via-induction-of-mir-1246-and-aromatase
#3
Sribalasubashini Muralimanoharan, Youn-Tae Kwak, Carole R Mendelson
Dysregulation of human trophoblast invasion and differentiation with placental hypoxia can result in preeclampsia, a hypertensive disorder of pregnancy. Herein, we characterized the role and regulation of miR-1246, which is markedly induced during human syncytiotrophoblast differentiation. miR-1246 is known to target GSK3β and AXIN2, inhibitors of WNT/β-catenin signaling, which is crucial for placental development, and is predicted to target JARID2, which promotes silencing of developmentally regulated genes...
March 13, 2018: Endocrinology
https://www.readbyqxmd.com/read/29499137/unique-structural-platforms-of-suz12-dictate-distinct-classes-of-prc2-for-chromatin-binding
#4
Siming Chen, Lianying Jiao, Murtada Shubbar, Xin Yang, Xin Liu
Developmentally regulated accessory subunits dictate PRC2 function. Here, we report the crystal structures of a 120 kDa heterotetrameric complex consisting of Suz12, Rbbp4, Jarid2, and Aebp2 fragments that is minimally active in nucleosome binding and of an inactive binary complex of Suz12 and Rbbp4. Suz12 contains two unique structural platforms that define distinct classes of PRC2 holo complexes for chromatin binding. Aebp2 and Phf19 compete for binding of a non-canonical C2 domain of Suz12; Jarid2 and EPOP occupy an overlapped Suz12 surface required for chromatin association of PRC2...
March 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29466914/inducible-crispr-genome-editing-platform-in-naive-human-embryonic-stem-cells-reveals-jarid2-function-in-self-renewal
#5
Amy Ferreccio, Julie Mathieu, Damien Detraux, Somasundaram Logeshwaran, Christopher Cavanaugh, Bryce Sopher, Karin Fischer, Thomas Bello, Assis M Hussein, Shiri Levy, Savannah Cook, Sonia B Sidhu, Filippo Artoni, Nathan J Palpant, Hans Reinecke, Yuliang Wang, Patrick Paddison, Charles Murry, Suman Jayadev, Carol Ware, Hannele Ruohola-Baker
To easily edit the genome of naïve human embryonic stem cells (hESC), we introduced a dual cassette encoding an inducible Cas9 into the AAVS1 site of naïve hESC (iCas9). The iCas9 line retained karyotypic stability, expression of pluripotency markers, differentiation potential, and stability in 5iLA and EPS pluripotency conditions. The iCas9 line induced efficient homology-directed repair (HDR) and non-homologous end joining (NHEJ) based mutations through CRISPR-Cas9 system. We utilized the iCas9 line to study the epigenetic regulator, PRC2 in early human pluripotency...
February 22, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29420179/jarid2-and-aebp2-mimic-histone-tails-to-promote-prc2-activity
#6
(no author information available yet)
Structures of PRC2 with its cofactors suggest context-dependent activation affected by cofactor binding.
March 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29374328/possible-effect-of-snail-family-transcriptional-repressor-1-polymorphisms-in-non-syndromic-cleft-lip-with-or-without-cleft-palate
#7
Francesca Cura, Annalisa Palmieri, Ambra Girardi, Francesco Carinci, Paolo Giovanni Morselli, Nayereh Nouri, Furio Pezzetti, Luca Scapoli, Marcella Martinelli
OBJECTIVE: Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state. MATERIALS AND METHODS: Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P...
January 27, 2018: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29348366/structures-of-human-prc2-with-its-cofactors-aebp2-and-jarid2
#8
Vignesh Kasinath, Marco Faini, Simon Poepsel, Dvir Reif, Xinyu Ashlee Feng, Goran Stjepanovic, Ruedi Aebersold, Eva Nogales
Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail...
February 23, 2018: Science
https://www.readbyqxmd.com/read/29232705/etv2-mir-130a-jarid2-cascade-regulates-vascular-patterning-during-embryogenesis
#9
Bhairab N Singh, Naoyuki Tahara, Yasuhiko Kawakami, Satyabrata Das, Naoko Koyano-Nakagawa, Wuming Gong, Mary G Garry, Daniel J Garry
Remodeling of the primitive vasculature is necessary for the formation of a complex branched vascular architecture. However, the factors that modulate these processes are incompletely defined. Previously, we defined the role of microRNAs (miRNAs) in endothelial specification. In the present study, we further examined the Etv2-Cre mediated ablation of DicerL/L and characterized the perturbed vascular patterning in the embryo proper and yolk-sac. We mechanistically defined an important role for miR-130a, an Etv2 downstream target, in the mediation of vascular patterning and angiogenesis in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29216786/a-study-of-single-nucleotide-polymorphisms-in-cd157-aim2-and-jarid2-genes-in-han-chinese-children-with-autism-spectrum-disorder
#10
Weiming Mo, Jun Liu, Zengyu Zhang, Hong Yu, Aiping Yang, Fei Qu, Pingfang Hu, Zhuo Liu, Fengpei Hu
PURPOSE: Autism spectrum disorder (ASD) is a group of developmental brain disorders caused by genetic and environmental factors. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes related to immune function were associated with ASD in Chinese Han children. MATERIALS AND METHODS: A total of 201 children with ASD and 200 age- and gender-matched healthy controls were recruited from September 2012 to June 2106. A TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698 and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2...
April 2018: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/29196338/proteomics-and-metabolomics-identify-molecular-mechanisms-of-aging-potentially-predisposing-for-chronic-lymphocytic-leukemia
#11
Rupert L Mayer, Josef D Schwarzmeier, Marlene C Gerner, Andrea Bileck, Johanna C Mader, Samuel M Meier-Menches, Samuel M Gerner, Klaus G Schmetterer, Tobias Pukrop, Albrecht Reichle, Astrid Slany, Christopher Gerner
B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, the chronic B cell leukemia cell line JVM-13 was also included. A principal component analysis comprising 6,945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells...
February 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29187421/identifying-genetic-differences-between-dongxiang-blue-shelled-and-white-leghorn-chickens-using-sequencing-data
#12
Qing-Bo Zhao, Rong-Rong Liao, Hao Sun, Zhe Zhang, Qi-Shan Wang, Chang-Suo Yang, Xiang-Zhe Zhang, Yu-Chun Pan
The Dongxiang Blue-shelled chicken is one of the most valuable Chinese indigenous poultry breeds. However, compared to the Italian native White Leghorn, although this Chinese breed possesses numerous favorable characteristics, it also exhibits lower growth performance and fertility. Here, we utilized genotyping sequencing data obtained via genome reduction on a sequencing platform to detect 100,114 single nucleotide polymorphisms and perform further biological analysis and functional annotation. We employed cross-population extended haplotype homozygosity, eigenvector decomposition combined with genome-wide association studies (EigenGWAS), and efficient mixed-model association expedited methods to detect areas of the genome that are potential selected regions (PSR) in both chicken breeds, and performed gene ontology (GO) enrichment and quantitative trait loci (QTL) analyses annotating using the Kyoto Encyclopedia of Genes and Genomes...
February 2, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29129997/trichloroethylene-induced-alterations-in-dna-methylation-were-enriched-in-polycomb-protein-binding-sites-in-effector-memory-cd4-t-cells
#13
Kathleen M Gilbert, Sarah J Blossom, Brad Reisfeld, Stephen W Erickson, Kanan Vyas, Mary Maher, Brannon Broadfoot, Kirk West, Shasha Bai, Craig A Cooney, Sudeepa Bhattacharyya
Exposure to industrial solvent and water pollutant trichloroethylene (TCE) can promote autoimmunity, and expand effector/memory (CD62L) CD4+ T cells. In order to better understand etiology reduced representation bisulfite sequencing was used to study how a 40-week exposure to TCE in drinking water altered methylation of ∼337 770 CpG sites across the entire genome of effector/memory CD4+ T cells from MRL+/+ mice. Regardless of TCE exposure, 62% of CpG sites in autosomal chromosomes were hypomethylated (0-15% methylation), and 25% were hypermethylated (85-100% methylation)...
July 2017: Environmental Epigenetics
https://www.readbyqxmd.com/read/29102770/overexpression-of-djmj-differentially-affects-intestinal-stem-cells-and-differentiated-enterocytes
#14
Dang Ngoc Anh Suong, Kouhei Shimaji, Jung-Hoon Pyo, Joung-Sun Park, Hideki Yoshida, Mi-Ae Yoo, Masamitsu Yamaguchi
Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo...
January 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29089047/whole-exome-sequencing-in-342-congenital-cardiac-left-sided-lesion-cases-reveals-extensive-genetic-heterogeneity-and-complex-inheritance-patterns
#15
Alexander H Li, Neil A Hanchard, Dieter Furthner, Susan Fernbach, Mahshid Azamian, Annarita Nicosia, Jill Rosenfeld, Donna Muzny, Lisa C A D'Alessandro, Shaine Morris, Shalini Jhangiani, Dhaval R Parekh, Wayne J Franklin, Mark Lewin, Jeffrey A Towbin, Daniel J Penny, Charles D Fraser, James F Martin, Christine Eng, James R Lupski, Richard A Gibbs, Eric Boerwinkle, John W Belmont
BACKGROUND: Left-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. METHODS: Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases...
October 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29058709/molecular-analysis-of-prc2-recruitment-to-dna-in-chromatin-and-its-inhibition-by-rna
#16
Xueyin Wang, Richard D Paucek, Anne R Gooding, Zachary Z Brown, Eva J Ge, Tom W Muir, Thomas R Cech
Many studies have revealed pathways of epigenetic gene silencing by Polycomb repressive complex 2 (PRC2) in vivo, but understanding the underlying molecular mechanisms requires biochemistry. Here we analyze interactions of reconstituted human PRC2 with nucleosome complexes. Histone modifications, the H3K27M cancer mutation, and inclusion of JARID2 or EZH1 in the PRC2 complex have unexpectedly minor effects on PRC2-nucleosome binding. Instead, protein-free linker DNA dominates the PRC2-nucleosome interaction...
December 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29048434/common-microrna-mrna-interactions-exist-among-distinct-porcine-ipsc-lines-independent-of-their-metastable-pluripotent-states
#17
Shiqiang Zhang, Youlong Xie, Hongxia Cao, Huayan Wang
Previous evidences have proved that porcine-induced pluripotent stem cells (piPSCs) could be induced to distinctive metastable pluripotent states. This raises the issue of whether there is a common transcriptomic profile existing among the piPSC lines at distinctive state. In this study, we performed conjoint analysis of small RNA-seq and mRNA-seq for three piPSC lines which represent LIF dependence, FGF2 dependence and LFB2i dependence, respectively. Interestingly, we found there are 16 common microRNAs which potentially target 13 common mRNAs among the three piPSC lines...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29046480/epigenetic-mechanisms-underlying-maternal-diabetes-associated-risk-of-congenital-heart-disease
#18
Madhumita Basu, Jun-Yi Zhu, Stephanie LaHaye, Uddalak Majumdar, Kai Jiao, Zhe Han, Vidu Garg
Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29044990/transcriptome-analysis-for-uvb-induced-phototoxicity-in-mouse-retina
#19
Mi-Jin An, Chul-Hong Kim, Gyu-You Nam, Dae-Hyun Kim, Sangmyung Rhee, Sung-Jin Cho, Jung-Woong Kim
Throughout life, the human eye is continuously exposed to sunlight and artificial lighting. Ambient light exposure can lead to visual impairment and transient or permanent blindness. To mimic benign light stress conditions, Mus musculus eyes were exposed to low-energy UVB radiation, ensuring no severe morphological changes in the retinal structure post-exposure. We performed RNA-seq analysis to reveal the early transcriptional changes and key molecular pathways involved before the activation of the canonical cell death pathway...
January 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/28912479/late-stage-differentiation-of-embryonic-pancreatic-%C3%AE-cells-requires-jarid2
#20
Sara Cervantes, Marta Fontcuberta-PiSunyer, Joan-Marc Servitja, Rebeca Fernandez-Ruiz, Ainhoa García, Lidia Sanchez, Young-Sook Lee, Ramon Gomis, Rosa Gasa
Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation...
September 14, 2017: Scientific Reports
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