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Epigenetic regulation of chromosome

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https://www.readbyqxmd.com/read/28532996/histone-methyltransferase-g9a-promotes-liver-cancer-development-by-epigenetic-silencing-of-tumor-suppressor-gene-rarres3
#1
Lai Wei, David Kung-Chun Chiu, Felice Ho-Ching Tsang, Dicky Cheuk-Ting Law, Carol Lai-Hung Cheng, Sandy Leung-Kuen Au, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. Epigenetic deregulation is a common trait of human HCC. G9s is an important epigenetics regulator. However, its roles in liver carcinogenesis remain to be investigated. METHODS: Gene expressions were determined by RNA-Seq and qRT-PCR. G9a knockdown and knockout cell lines were established by lentiviral-based shRNA and CRISPR/Cas9 gene editing system. Tumor promoting functions of G9a was studied by both in HCC cell lines and nude mice model...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28523538/mecp2-a-modulator-of-neuronal-chromatin-organization-involved-in-rett-syndrome
#2
Alexia Martínez de Paz, Juan Ausió
From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28512193/dna-replication-timing-during-development-anticipates-transcriptional-programs-and-parallels-enhancer-activation
#3
Joseph C Siefert, Constantin Georgescu, Jonathan D Wren, Amnon Koren, Christopher L Sansam
In dividing cells, DNA replication occurs in a precise order, but many questions remain regarding the mechanisms of replication timing establishment and regulation. We now have generated genome-wide, high-resolution replication timing maps throughout zebrafish development. Unexpectedly, in the rapid cell cycles preceding the midblastula transition, a defined timing program was present that predicted the initial wave of zygotic transcription. Replication timing was thereafter progressively and continuously remodeled across the majority of the genome, and epigenetic changes involved in enhancer activation frequently paralleled developmental changes in replication timing...
May 16, 2017: Genome Research
https://www.readbyqxmd.com/read/28502113/epigenetic-modifications-of-the-vh-region-after-djh-recombination-in-pro-b-cells
#4
Yanying Dong, Caijun Wu, Xiaohui Zhao, Ping Zhang, Hua Zhang, Mingzhe Zheng, Shichang Li, Junna Jiao, Xiaozhuo Yu, Zhuangwei Lv, Yanhong Ji
The variable region of murine immunoglobulin heavy chain (Igh) is assembled by sequential DH -JH and VH -DJH recombination. The accessibility of Igh locus determines the order of rearrangement. Because of the large number of VH genes and lack of a suitable model, the epigenetic modifications of VH genes after DJH recombination have not previously been characterized. Here, we employed two v-Abl pro-B cell lines, in which Igh locus is in germline and DJH -recombined configuration, respectively. The DJH junction displays the characteristics of recombination center, such as high levels of activation-associated histone modifications and recombination activating gene protein (RAG) binding in DJH -rearranged pro-B cells, which extend the recombination center model proposed for germline Igh locus...
May 14, 2017: Immunology
https://www.readbyqxmd.com/read/28501516/is-dual-inhibition-of-metalloenzymes-hdac-8-and-mmp-2-a-potential-pharmacological-target-to-combat-hematological-malignancies
#5
REVIEW
Sk Abdul Amin, Nilanjan Adhikari, Tarun Jha
For the last three decades, metalloenzymes such as histone deacetylases (HDACs) and matrix metalloproteinases (MMPs) have been identified in promoting solid as well as hematological carcinogenesis. Histone deacetylase 8 (HDAC-8), a class I HDAC enzyme, may serve as 'epigenetic player' that affects in the regulation of transcription factors and alters the structure of chromosome associated with tumorigenesis. It is established that the influence of MMP-2 in invasion, metastasis and angiogenenic events of hematological malignancies may be suppressed by HDAC inhibitors through reversion-inducing-cysteine-rich protein with kazal motifs (RECK) protein...
May 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28486493/characterization-of-joining-sites-of-a-viral-histone-h4-on-host-insect-chromosomes
#6
Sunil Kumar, Jin-Kyo Jung, Yonggyun Kim
A viral histone H4 (CpBV-H4) is encoded in a polydnavirus, Cotesia plutellae bracovirus (CpBV). It plays a crucial role in parasitism of an endoparasitoid wasp, C. plutellae, against diamondback moth, Plutella xylostella, by altering host gene expression in an epigenetic mode by its N-terminal tail after joining host nucleosomes. Comparative transcriptomic analysis between parasitized and nonparasitized P. xylostella by RNA-Seq indicated that 1,858 genes were altered at more than two folds in expression levels at late parasitic stage, including 877 up-regulated genes and 981 down-regulated genes...
2017: PloS One
https://www.readbyqxmd.com/read/28485726/gene-body-5-hydroxymethylation-is-associated-with-gene-expression-changes-in-the-prefrontal-cortex-of-depressed-individuals
#7
J A Gross, A Pacis, G G Chen, M Drupals, P-E Lutz, L B Barreiro, G Turecki
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19)...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28478949/imprinted-disorders-and-growth
#8
Éloïse Giabicani, Frédéric Brioude, Yves Le Bouc, Irène Netchine
Fetal growth is a complex process. Its restriction is associated with morbidity and long-term metabolic consequences. Imprinted genes have a critical role in mammalian fetal growth. Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two imprinting disorders with opposite fetal growth disturbance. SRS is leading to severe fetal and postnatal growth retardation with severe feeding difficulties during early childhood and long-term metabolic consequences and BWS is an overgrowth syndrome with an enhanced risk of tumors during childhood...
May 4, 2017: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28471386/transposable-elements-in-human-cancer-causes-and-consequences-of-deregulation
#9
REVIEW
Sumadi Lukman Anwar, Wahyu Wulaningsih, Ulrich Lehmann
Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications...
May 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28468239/choline-other-methyl-donors-and-epigenetics
#10
Steven Zeisel
Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations...
April 29, 2017: Nutrients
https://www.readbyqxmd.com/read/28467969/analysis-of-bos-taurus-and-sus-scrofa-x-and-y-chromosome-transcriptome-highlights-reproductive-driver-genes
#11
Faheem Ahmed Khan, Hui Liu, Hao Zhou, Kai Wang, Muhammad Tahir Ul Qamar, Nuruliarizki Shinta Pandupuspitasari, Zhang Shujun
The biology of sperm, its capability of fertilizing an egg and its role in sex ratio are the major biological questions in reproductive biology. To answer these question we integrated X and Y chromosome transcriptome across different species: Bos taurus and Sus scrofa and identified reproductive driver genes based on Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm. Our strategy resulted in 11007 and 10445 unique genes consisting of 9 and 11 reproductive modules in Bos taurus and Sus scrofa, respectively...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28460450/epigenetically-altered-mir-1247-functions-as-a-tumor-suppressor-in-pancreatic-cancer
#12
Joo Mi Yi, Eun-Jin Kang, Hyun-Mi Kwon, Jin-Han Bae, Keunsoo Kang, Nita Ahuja, Kwangmo Yang
Altered expression of microRNAs has been strongly implicated in human cancers, and growing evidence is emerging that a number of miRNAs are downregulated in cancer associated with CpG island hypermethylation. Although pancreatic cancer is one of the most malignant human cancers, the roles of miRNAs underlying the tumorigenesis of pancreatic cancer are still poorly understood. In the present study, we explored the molecular functional role of microRNA-1247 as tumor suppressor associated with epigenetic alteration in pancreatic cancer...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28452984/frequent-somatic-mutations-in-epigenetic-regulators-in-newly-diagnosed-chronic-myeloid-leukemia
#13
E Togasaki, J Takeda, K Yoshida, Y Shiozawa, M Takeuchi, M Oshima, A Saraya, A Iwama, K Yokote, E Sakaida, C Hirase, A Takeshita, K Imai, H Okumura, Y Morishita, N Usui, N Takahashi, S Fujisawa, Y Shiraishi, K Chiba, H Tanaka, H Kiyoi, K Ohnishi, S Ohtake, N Asou, Y Kobayashi, Y Miyazaki, S Miyano, S Ogawa, I Matsumura, C Nakaseko, T Naoe
Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17)...
April 28, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28447382/quantitative-proteomic-analysis-of-ezh2-inhibition-in-acute-myeloid-leukemia-reveals-the-targets-and-pathways-that-precede-the-induction-of-cell-death
#14
Jarrod J Sandow, Giuseppe Infusini, Aliaksei Z Holik, Gabriela Brumatti, Tessa V Averink, Paul G Ekert, Andrew I Webb
PURPOSE: Chromosomal translocation of the Mixed Lineage Leukemia (MLL) locus generates fusion proteins that drive acute myeloid leukemia (AML) resulting in atypical histone methyltransferase activity and alterations in the epigenetic regulation of gene expression. Targeting histone regulators, such as Enhancer of Zeste Homologue 2 (EZH2), has shown promise in AML. Profiling differential protein expression following inhibition of epigenetic regulators in AML may help to identify novel targets for therapeutics...
April 26, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28442993/alcohol-induced-neuroadaptation-is-orchestrated-by-the-histone-acetyltransferase-cbp
#15
Alfredo Ghezzi, Xiaolei Li, Linda K Lew, Thilini P Wijesekera, Nigel S Atkinson
Homeostatic neural adaptations to alcohol underlie the production of alcohol tolerance and the associated symptoms of withdrawal. These adaptations have been shown to persist for relatively long periods of time and are believed to be of central importance in promoting the addictive state. In Drosophila, a single exposure to alcohol results in long-lasting alcohol tolerance and symptoms of withdrawal following alcohol clearance. These persistent adaptations involve mechanisms such as long-lasting changes in gene expression and perhaps epigenetic restructuring of chromosomal regions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28439531/genome-and-cd4-t-cell-methylome-wide-association-study-of-circulating-trimethylamine-n-oxide-in-the-genetics-of-lipid-lowering-drugs-and-diet-network-goldn
#16
Stella Aslibekyan, Marguerite R Irvin, Bertha A Hidalgo, Rodney T Perry, Elias J Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N Hopkins, Michael A Province, Hemant K Tiwari, Jose M Ordovas, Devin M Absher, Donna K Arnett
BACKGROUND: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels. METHODS AND RESULTS: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans...
June 2017: Journal of Nutrition & Intermediary Metabolism
https://www.readbyqxmd.com/read/28436605/digeorge-like-syndrome-in-a-child-with-a-3p12-3-deletion-involving-mir4273-gene-born-to-a-mother-with-gestational-diabetes-mellitus
#17
Emilia Cirillo, Giuliana Giardino, Vera Gallo, Giovanni Galasso, Roberta Romano, Roberta D'Assante, Giulia Scalia, Luigi Del Vecchio, Lucio Nitsch, Rita Genesio, Claudio Pignata
Chromosome 22q11.2 deletion is the most common chromosomal alteration associated with DiGeorge syndrome (DGS), even though this is not the only underlying cause of DGS. In rare patients, mutations in a single gene, TBX1, have been described resulting in a DGS phenotype. Recently, it has been reported that at least part of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins (BMP) signaling. Evidence suggests that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and Bmp-signaling...
April 24, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28433382/applications-of-the-crispr-cas9-system-in-kidney-research
#18
REVIEW
Yoshiki Higashijima, Seiichi Hirano, Masaomi Nangaku, Osamu Nureki
The recently discovered clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) is an RNA-guided DNA nuclease, and has been harnessed for the development of simple, efficient, and relatively inexpensive technologies to precisely manipulate the genomic information in virtually all cell types and organisms. The CRIPSR-Cas9 systems have already been effectively used to disrupt multiple genes simultaneously, create conditional alleles, and generate reporter proteins, even in vivo...
April 19, 2017: Kidney International
https://www.readbyqxmd.com/read/28424341/alterations-in-three-dimensional-organization-of-the-cancer-genome-and-epigenome
#19
Joanna Achinger-Kawecka, Phillippa C Taberlay, Susan J Clark
The structural and functional basis of the genome is provided by the three-dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer elements and promoter regions are brought into close spatial proximity to ensure proper, cell type-specific gene expression. In cancer, genetic and epigenetic processes can deregulate the transcriptional program. To investigate whether the 3D chromatin state is also disrupted in cancer we performed Hi-C chromosome conformation sequencing in normal and prostate cancer cells and compared the chromatin interaction maps with changes to the genome and epigenome...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28377371/molecular-basis-for-cdk1-regulated-timing-of-mis18-complex-assembly-and-cenp-a-deposition
#20
Frances Spiller, Bethan Medina-Pritchard, Maria Alba Abad, Martin A Wear, Oscar Molina, William C Earnshaw, A Arockia Jeyaprakash
The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex...
April 4, 2017: EMBO Reports
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