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https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#1
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27894241/a-novel-relationship-for-schizophrenia-bipolar-and-major-depressive-disorder-part-6-a-hint-from-chromosome-6-high-density-association-screen
#2
X Chen, F Long, B Cai, X Chen, G Chen
Convergent evidence from genetics, symptomatology and psychopharmacology imply that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD), for example, any two or even three of these disorders could co-exist in some families. A total of 56.400 single nucleotide polymorphism (SNPs) on chromosome 6 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type-I), 177 MDD patients and 1000 controls. Associated SNP loci on chromosome 6 were comprehensively revealed and outstanding susceptibility genes were identified including JARID2 (Homo sapiens jumonji, AT rich interactive domain 2) which plays an essential role in embryonic development and neural tube fusion process...
November 28, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27892467/jarid2-binds-mono-ubiquitylated-h2a-lysine-119-to-mediate-crosstalk-between-polycomb-complexes-prc1-and-prc2
#3
Sarah Cooper, Anne Grijzenhout, Elizabeth Underwood, Katia Ancelin, Tianyi Zhang, Tatyana B Nesterova, Burcu Anil-Kirmizitas, Andrew Bassett, Susanne M Kooistra, Karl Agger, Kristian Helin, Edith Heard, Neil Brockdorff
The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27852821/meg3-long-noncoding-rna-contributes-to-the-epigenetic-regulation-of-epithelial-mesenchymal-transition-in-lung-cancer-cell-lines
#4
Minoru Terashima, Shoichiro Tange, Akihiko Ishimura, Takeshi Suzuki
Histone methylation is implicated in a number of biological and pathological processes including cancer development. In this study, we investigated the molecular mechanism for the recruitment of Polycomb repressive complex-2 (PRC2) and its accessory component, JARID2, to chromatin, which regulates methylation of lysine 27 of histone H3 (H3K27), during epithelial-mesenchymal transition (EMT) of cancer cells. The expression of MEG3 long noncoding RNA (lncRNA), which could interact with JARID2, was clearly increased during Transforming Growth Factor-beta (TGF-β)-induced EMT of human lung cancer cell lines...
November 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27760138/family-based-whole-exome-sequencing-reveals-the-multifaceted-role-of-notch-signaling-in-congenital-heart-disease
#5
Christoph Preuss, Melanie Capredon, Florian Wünnemann, Philippe Chetaille, Andrea Prince, Beatrice Godard, Severine Leclerc, Nara Sobreira, Hua Ling, Philip Awadalla, Maryse Thibeault, Paul Khairy, Mark E Samuels, Gregor Andelfinger
Left-ventricular outflow tract obstructions (LVOTO) encompass a wide spectrum of phenotypically heterogeneous heart malformations which frequently cluster in families. We performed family based whole-exome and targeted re-sequencing on 182 individuals from 51 families with multiple affected members. Central to our approach is the family unit which serves as a reference to identify causal genotype-phenotype correlations. Screening a multitude of 10 overlapping phenotypes revealed disease associated and co-segregating variants in 12 families...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27748065/intragenic-cnvs-for-epigenetic-regulatory-genes-in-intellectual-disability-survey-identifies-pathogenic-and-benign-single-exon-changes
#6
Farah R Zahir, Tracy Tucker, Sonia Mayo, Carolyn J Brown, Emilia L Lim, Jonathan Taylor, Marco A Marra, Fadi F Hamdan, Jacques L Michaud, Jan M Friedman
The disruption of genes involved in epigenetic regulation is well known to cause Intellectual Disability (ID). We reported a custom microarray study that interrogated among others, the epigenetic regulatory gene-class, at single exon resolution. Here we elaborate on identified intragenic CNVs involving epigenetic regulatory genes; specifically discussing those in three genes previously unreported in ID etiology-ARID2, KDM3A, and ARID4B. The changes in ARID2 and KDM3A are likely pathogenic while the ARID4B variant is uncertain...
November 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27641964/reduced-expression-of-jumonji-at-rich-interactive-domain-2-jarid2-in-glioma-inhibits-tumor-growth-in-vitro-and-in-vivo
#7
Zhenjiang Li, Chenyang Xu, Ming Gao, Bingqian Ding, Xinting Wei, Nan Ji
Jumonji AT-rich interactive domain 2 (JARID2) is a member of the Jumonji family of proteins and has been proposed as an oncogene in several types of human cancer. However, the role of JARID2 in human glioma has not yet been understood. The present study was designed to determine the roles of JARID2 in the proliferation and migration in human glioma cells and the growth of glioma cells in nude mice. Our data indicate that JARID2 is up-regulated in human glioma tissues and cell lines. Knockdown of JARID2 obviously inhibits the proliferation of U87MG cells and tumor growth in vivo...
September 16, 2016: Oncology Research
https://www.readbyqxmd.com/read/27620904/high-diagnostic-yield-of-syndromic-intellectual-disability-by-targeted-next-generation-sequencing
#8
Francisco Martínez, Alfonso Caro-Llopis, Mónica Roselló, Silvestre Oltra, Sonia Mayo, Sandra Monfort, Carmen Orellana
BACKGROUND: Intellectual disability is a very complex condition where more than 600 genes have been reported. Due to this extraordinary heterogeneity, a large proportion of patients remain without a specific diagnosis and genetic counselling. The need for new methodological strategies in order to detect a greater number of mutations in multiple genes is therefore crucial. METHODS: In this work, we screened a large panel of 1256 genes (646 pathogenic, 610 candidate) by next-generation sequencing to determine the molecular aetiology of syndromic intellectual disability...
September 12, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/27475236/an-integrative-approach-predicted-co-expression-sub-networks-regulating-properties-of-stem-cells-and-differentiation
#9
Mousumi Sahu, Bibekanand Mallick
The differentiation of human Embryonic Stem Cells (hESCs) is accompanied by the formation of different intermediary cells, gradually losing its stemness and acquiring differentiation. The precise mechanisms underlying hESCs integrity and its differentiation into fibroblast (Fib) are still elusive. Here, we aimed to assess important genes and co-expression sub-networks responsible for stemness, early differentiation of hESCs into embryoid bodies (EBs) and its lineage specification into Fibs. To achieve this, we compared transcriptional profiles of hESCs-EBs and EBs-Fibs and obtained differentially expressed genes (DEGs) exclusive to hESCs-EBs (early differentiation), EBs-Fibs (late differentiation) and common DEGs in hESCs-EBs and EBs-Fibs...
July 18, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27405055/cardiac-defects-nuchal-edema-and-abnormal-lymphatic-development-are-not-associated-with-morphological-changes-in-the-ductus-venosus
#10
Nicole B Burger, Monique C Haak, Evelien Kok, Christianne J M de Groot, Weinian Shou, Peter J Scambler, Youngsook Lee, Eunjin Cho, Vincent M Christoffels, Mireille N Bekker
BACKGROUND: In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac function or are caused by local morphological alterations in the ductus venosus. AIM: The aim of this study was to investigate if the observed increased nuchal translucency, cardiac defects and abnormal lymphatic development in the examined mouse models are associated with local changes in ductus venosus morphology...
October 2016: Early Human Development
https://www.readbyqxmd.com/read/27363682/genome-wide-association-study-identifies-multiple-susceptibility-loci-for-multiple-myeloma
#11
Jonathan S Mitchell, Ni Li, Niels Weinhold, Asta Försti, Mina Ali, Mark van Duin, Gudmar Thorleifsson, David C Johnson, Bowang Chen, Britt-Marie Halvarsson, Daniel F Gudbjartsson, Rowan Kuiper, Owen W Stephens, Uta Bertsch, Peter Broderick, Chiara Campo, Hermann Einsele, Walter A Gregory, Urban Gullberg, Marc Henrion, Jens Hillengass, Per Hoffmann, Graham H Jackson, Ellinor Johnsson, Magnus Jöud, Sigurður Y Kristinsson, Stig Lenhoff, Oleg Lenive, Ulf-Henrik Mellqvist, Gabriele Migliorini, Hareth Nahi, Sven Nelander, Jolanta Nickel, Markus M Nöthen, Thorunn Rafnar, Fiona M Ross, Miguel Inacio da Silva Filho, Bhairavi Swaminathan, Hauke Thomsen, Ingemar Turesson, Annette Vangsted, Ulla Vogel, Anders Waage, Brian A Walker, Anna-Karin Wihlborg, Annemiek Broyl, Faith E Davies, Unnur Thorsteinsdottir, Christian Langer, Markus Hansson, Martin Kaiser, Pieter Sonneveld, Kari Stefansson, Gareth J Morgan, Hartmut Goldschmidt, Kari Hemminki, Björn Nilsson, Richard S Houlston
Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10(-8)), 6q21 (rs9372120, P=9...
2016: Nature Communications
https://www.readbyqxmd.com/read/27328068/brazilian-multicenter-study-of-association-between-polymorphisms-in-crispld2-and-jarid2-and-non-syndromic-oral-clefts
#12
Ana Camila Messetti, Renato Assis Machado, Carine Ervolino de Oliveira, Hercílio Martelli-Júnior, Silvia Regina de Almeida Reis, Helenara Salvati Bertolossi Moreira, Darlene Camati Persuhn, Tao Wu, Ricardo D Coletta
BACKGROUND: Variants in the cysteine-rich secretory protein LCCL domain containing 2 gene (CRISPLD2) and in the jumonji, AT-rich interaction domain 2 gene (JARID2) were previously shown to influence non-syndromic oral cleft susceptibility. Herein, we performed a case-control study to examine the potential association of single-nucleotide polymorphisms (SNPs) in CRISPLD2 and JARID2 with non-syndromic cleft lip and/or palate (NSCL/P) in the Brazilian population. Given the ethnicity-dependent genetic predisposition to NSCL/P, we performed a structured analysis taking into account the genomic ancestry variation of each individual...
June 21, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27259236/jarid2-promotes-invasion-and-metastasis-of-hepatocellular-carcinoma-by-facilitating-epithelial-mesenchymal-transition-through-pten-akt-signaling
#13
Xiong Lei, Jiang-Feng Xu, Rui-Min Chang, Feng Fang, Chao-Hui Zuo, Lian-Yue Yang
JARID2 is crucial for maintenance of pluripotency and differentiation of embryonic stem cells. However, little is known about the role of JARID2 in metastasis of hepatocellular carcinoma (HCC). This study found that JARID2 expression was significantly higher in HCC tissues than that in adjacent non-tumor liver tissues (ANLTs), and its expression level correlated with HCC metastasis. High JARID2 expression was significantly correlated with multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27170560/identification-of-genetic-variants-associated-with-susceptibility-to-west-nile-virus-neuroinvasive-disease
#14
D Long, X Deng, P Singh, M Loeb, A S Lauring, M Seielstad
West Nile virus (WNV) infection results in a diverse spectrum of outcomes, and host genetics are likely to influence susceptibility to neuroinvasive disease (West Nile neuroinvasive disease (WNND)). We performed whole-exome sequencing of 44 individuals with WNND and identified alleles associated with severe disease by variant filtration in cases, kernel association testing in cases and controls and single-nucleotide polymorphism (SNP) imputation into a larger cohort of WNND cases and seropositive controls followed by genome-wide association analysis...
July 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27102007/expression-of-anril-polycomb-complexes-cdkn2a-b-arf-genes-in-breast-tumors-identification-of-a-two-gene-ezh2-cbx7-signature-with-independent-prognostic-value
#15
Didier Meseure, Sophie Vacher, Kinan Drak Alsibai, Andre Nicolas, Walid Chemlali, Martial Caly, Rosette Lidereau, Eric Pasmant, Celine Callens, Ivan Bieche
UNLABELLED: ANRIL, a long noncoding RNA (lncRNA), has recently been reported to have a direct role in recruiting polycomb repressive complexes PRC2 and PRC1 to regulate the expression of the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster. Expression analysis of ANRIL, EZH2, SUZ12, EED, JARID2, CBX7, BMI1, p16, p15, and p14/ARF genes was evaluated in a large cohort of invasive breast carcinomas (IBC, n = 456) by qRT-PCR and immunohistochemistry (IHC) was performed on CBX7, EZH2, p14, p15, p16, H3K27me3, and H3K27ac...
July 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27012147/inhibiting-smad2-3-signaling-in-pluripotent-mouse-embryonic-stem-cells-enhances-endoderm-formation-by-increasing-transcriptional-priming-of-lineage-specifying-target-genes
#16
Øyvind Dahle, Michael R Kuehn
BACKGROUND: Pluripotent embryonic stem cells (ESCs) offer great potential for regenerative medicine. However, efficient in vitro generation of specific desired cell types is still a challenge. We previously established that Smad2/3 signaling, essential for endoderm formation, regulates target gene expression by counteracting epigenetic repression mediated by Polycomb Repressive Complex 2 (PRC2). Although this mechanism has been demonstrated during differentiation and reprogramming, little is known of its role in pluripotent cells...
July 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/26938987/involvement-of-polycomb-repressive-complex-2-in-maturation-of-induced-pluripotent-stem-cells-during-reprogramming-of-mouse-and-human-fibroblasts
#17
Niusha Khazaie, Mohammad Massumi, Ping Wee, Mahdieh Salimi, Abdulshakour Mohammadnia, Moein Yaqubi
Induced pluripotent stem cells (iPSCs) provide a reliable source for the study of regenerative medicine, drug discovery, and developmental biology. Despite extensive studies on the reprogramming of mouse and human fibroblasts into iPSCs, the efficiency of reprogramming is still low. Here, we used a bioinformatics and systems biology approach to study the two gene regulatory waves governing the reprogramming of mouse and human fibroblasts into iPSCs. Our results revealed that the maturation phase of reprogramming was regulated by a more complex regulatory network of transcription factors compared to the initiation phase...
2016: PloS One
https://www.readbyqxmd.com/read/26657861/microrna-155-controls-affinity-based-selection-by-protecting-c-myc-b-cells-from-apoptosis
#18
Rinako Nakagawa, Rebecca Leyland, Michael Meyer-Hermann, Dong Lu, Martin Turner, Giuseppina Arbore, Tri Giang Phan, Robert Brink, Elena Vigorito
The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood...
January 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26657856/molecular-fine-tuning-of-affinity-maturation-in-germinal-centers
#19
COMMENT
Yee Ling Wu, Cristina Rada
The development of high-affinity antibodies in response to infection is an iterative process in which B cells cycle between proliferation/somatic hypermutation and antigen-driven selection. These processes occur within specific regions of the secondary lymphoid structures known as germinal centers (GCs) and the environmental and signaling cues provided by these regions guide the GC reactions that drive B cell maturation and antibody production, ultimately determining B cell fate. In this issue of the JCI, Nakagawa and colleagues examine the role of miR-155, a microRNA that is required for GC development and the production of high-affinity antibodies...
January 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26523946/combined-overexpression-of-jarid2-prdm14-esrrb-and-sall4a-dramatically-improves-efficiency-and-kinetics-of-reprogramming-to-induced-pluripotent-stem-cells
#20
Hiroyoshi Iseki, Yutaka Nakachi, Tomoaki Hishida, Yzumi Yamashita-Sugahara, Masataka Hirasaki, Atsushi Ueda, Yoko Tanimoto, Saori Iijima, Fumihiro Sugiyama, Ken-ichi Yagami, Satoru Takahashi, Akihiko Okuda, Yasushi Okazaki
Identification of a gene set capable of driving rapid and proper reprogramming to induced pluripotent stem cells (iPSCs) is an important issue. Here we show that the efficiency and kinetics of iPSC reprogramming are dramatically improved by the combined expression of Jarid2 and genes encoding its associated proteins. We demonstrate that forced expression of JARID2 promotes iPSC reprogramming by suppressing the expression of Arf, a known reprogramming barrier, and that the N-terminal half of JARID2 is sufficient for such promotion...
February 2016: Stem Cells
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