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https://read.qxmd.com/read/30767315/molecularly-confirmed-kabuki-niikawa-kuroki-syndrome-patients-demonstrate-a-specific-cognitive-profile-with-extensive-visuospatial-abnormalities
#1
J Harris, E M Mahone, H T Bjornsson
BACKGROUND: Kabuki (Niikawa-Kuroki) syndrome (KS) is caused by disease-causing variants in either of two components (KMT2D and KDM6A) of the histone methylation machinery. Nearly all individuals with KS have cognitive difficulties, and most have intellectual disability. Recent studies on a mouse model of KS suggest disruption of normal adult neurogenesis in the granule cell layer of the dentate gyrus of the hippocampus. These mutant mice also demonstrate hippocampal memory defects compared with littermates, but this phenotype is rescued postnatally with agents that target the epigenetic machinery...
February 14, 2019: Journal of Intellectual Disability Research: JIDR
https://read.qxmd.com/read/30762097/allyl-isothiocyanate-regulates-lysine-acetylation-and-methylation-marks-in-an-experimental-model-of-malignant-melanoma
#2
Melina Mitsiogianni, Theodora Mantso, Dimitrios T Trafalis, H P Vasantha Rupasinghe, Vasilis Zoumpourlis, Rodrigo Franco, Sotiris Botaitis, Aglaia Pappa, Mihalis I Panayiotidis
OBJECTIVE(S): Isothiocyanates (ITCs) are biologically active plant secondary metabolites capable of mediating various biological effects including modulation of the epigenome. Our aim was to characterize the effect of allyl isothiocyanate (AITC) on lysine acetylation and methylation marks as a potential epigenetic-induced anti-melanoma strategy. METHODS: Our malignant melanoma model consisted of (1) human (A375) and murine (B16-F10) malignant melanoma as well as of human; (2) brain (VMM1) and lymph node (Hs 294T) metastatic melanoma; (3) non-melanoma epidermoid carcinoma (A431) and (4) immortalized keratinocyte (HaCaT) cells subjected to AITC...
February 14, 2019: European Journal of Nutrition
https://read.qxmd.com/read/30746694/decoding-genetic-and-epigenetic-information-embedded-in-cell-free-dna-with-adapted-salp-seq
#3
Jian Wu, Wei Dai, Lin Wu, Weiwei Li, Xinyi Xia, Jinke Wang
Cell free DNA (cfDNA) in human plasma carries abundant information, which has therefore been the key sample for non-invasive prenatal testing (NIPT) and liquid biopsy. Especially by using the rapidly developed next-generation sequencing (NGS) techniques, the genetic and epigenetic information embedded in cfDNA has been effectively and extensively decoded. In this process, a key step is to construct the NGS library. Due to its high degradation, the single strand-based method was reported to be more qualified to construct the NGS library of cfDNA...
February 12, 2019: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/30742097/downregulation-of-specific-fbxw7-isoforms-with-differential-effects-in-t-cell-lymphoblastic-lymphoma
#4
Irene Vázquez-Domínguez, Laura González-Sánchez, Pilar López-Nieva, Pablo Fernández-Navarro, María Villa-Morales, María Á Cobos-Fernández, Isabel Sastre, Mario F Fraga, Agustín F Fernández, Marcos Malumbres, María Salazar-Roa, Osvaldo Graña-Castro, Javier Santos, Pilar Llamas, José L López-Lorenzo, José Fernández-Piqueras
FBXW7 is a driver gene in T-cell lymphoblastic neoplasia acting through proteasome degradation of key proto-oncogenes. FBXW7 encodes three isoforms, α, β and γ, which differ only in the N-terminus. In this work, massive sequencing revealed significant downregulation of FBXW7 in a panel of primary T-cell lymphoblastic lymphomas characterised by the absence of mutations in its sequence. We observed that decreased expression mainly affected the FBXW7β isoform and to a lesser extent FBXW7α and may be attributed to the combined effect of epigenetic changes, alteration of upstream factors and upregulation of miRNAs...
February 11, 2019: Oncogene
https://read.qxmd.com/read/30738111/on-top-of-biosynthetic-gene-clusters-how-epigenetic-machinery-influences-secondary-metabolism-in-fungi
#5
REVIEW
Brandon T Pfannenstiel, Nancy P Keller
Fungi produce an abundance of bioactive secondary metabolites which can be utilized as antibiotics and pharmaceutical drugs. The genes encoding secondary metabolites are contiguously arranged in biosynthetic gene clusters (BGCs), which supports co-regulation of all genes required for any one metabolite. However, an ongoing challenge to harvest this fungal wealth is the finding that many of the BGCs are 'silent' in laboratory settings and lie in heterochromatic regions of the genome. Successful approaches allowing access to these regions - in essence converting the heterochromatin covering BGCs to euchromatin - include use of epigenetic stimulants and genetic manipulation of histone modifying proteins...
February 6, 2019: Biotechnology Advances
https://read.qxmd.com/read/30733618/dementia-in-down-syndrome-unique-insights-for-alzheimer-disease-research
#6
REVIEW
Ira T Lott, Elizabeth Head
Virtually all adults with Down syndrome (DS) show the neuropathological changes of Alzheimer disease (AD) by the age of 40 years. This association is partially due to overexpression of amyloid precursor protein, encoded by APP, as a result of the location of this gene on chromosome 21. Amyloid-β accumulates in the brain across the lifespan of people with DS, which provides a unique opportunity to understand the temporal progression of AD and the epigenetic factors that contribute to the age of dementia onset...
February 7, 2019: Nature Reviews. Neurology
https://read.qxmd.com/read/30721543/cooperation-of-pu-1-with-irf8-and-nfatc1-defines-chromatin-landscapes-during-rankl-induced-osteoclastogenesis
#7
Naohiro Izawa, Daisuke Kurotaki, Seitaro Nomura, Takanori Fujita, Yasunori Omata, Tetsuro Yasui, Jun Hirose, Takumi Matsumoto, Taku Saito, Yuho Kadono, Hiroyuki Okada, Takeshi Miyamoto, Tomohiko Tamura, Hiroyuki Aburatani, Sakae Tanaka
Receptor activator of nuclear factor κB ligand (RANKL) induces osteoclast (OC) differentiation from bone marrow-derived macrophages (BMMs). The transcription factors nuclear factor of activated T cells 1 (NFATc1) and interferon regulatory factor (IRF) 8 play positive and negative roles, respectively, in this process. However, genome-wide mapping of the active cis-regulatory elements regulating OC differentiation has not been performed, and little is known about the global landscape of OC-specific gene regulation...
February 5, 2019: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://read.qxmd.com/read/30711808/simultaneous-quantitation-of-14-dna-alkylation-adducts-in-human-liver-and-kidney-cells-by-uhplc-ms-ms-application-to-profiling-dna-adducts-of-genotoxic-reagents
#8
Yu Tang, Zhe Wang, Menglin Li, Ruiping Zhang, Jinlan Zhang
A rapid, sensitive and wide coverage ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous quantitation of 14 alkylation DNA adducts in cell genomic DNA, RNA and cell contents isolated from the in vitro cultured human kidney cell line 293 T and the human liver cell line L02 exposed to 3 genotoxic reagents: N-methyl-N-nitrosourea (MNU), methyl methanesulfonate (MMS) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)...
January 25, 2019: Journal of Pharmaceutical and Biomedical Analysis
https://read.qxmd.com/read/30703747/liver-pathology-in-wilson-s-disease-from-copper-overload-to-cirrhosis
#9
C Gerosa, D Fanni, T Congiu, M Piras, F Cau, M Moi, G Faa
Wilson's disease (WD) is a genetic metabolic disease strictly associated with liver cirrhosis. In this review, the genetic bases of the disease are discussed, with emphasis on the role of ATP7B (the Wilson disease protein) dysfunction as a determinant factor of systemic copper overload. Regarding the different multiple mutations described in WD patients, the peculiarity of Sardinian population is highlighted, Sardinians carrying a rare deletion in the promoter (5' UTR) of the WD gene. The role of epigenetic changes in the clinical presentation and evolution of liver disease in WD patients is also discussed, nutrition probably representing a relevantly risk factor in WD patients...
January 15, 2019: Journal of Inorganic Biochemistry
https://read.qxmd.com/read/30702368/a-droplet-digital-pcr-assay-for-smoking-predicts-all-cause-mortality
#10
Allan M Andersen, Philip T Ryan, Fredrick X Gibbons, Ronald L Simons, Jeffrey D Long, Robert A Philibert
OBJECTIVES: -Determine whether an epigenetic assay for smoking predicts all-cause mortality in adults participating in a longitudinal study of Iowa adoptees. BACKGROUND: -Improved biomarkers for smoking are needed given its large public health impact and significant limitations of both self-report and current biomarkers, such as cotinine in detecting smoking. In the past 5 years, multiple epigenome-wide association studies of smoking have identified loci suitable for translation as epigenetic biomarkers for smoking, in particular the CpG cg05575921...
January 31, 2019: Journal of Insurance Medicine
https://read.qxmd.com/read/30698829/the-contribution-of-active-and-passive-mechanisms-of-5mc-and-5hmc-removal-in-human-t-lymphocytes-is-differentiation-and-activation-dependent
#11
Lucia Vincenzetti, Cristina Leoni, Michele Chirichella, Ivo Kwee, Silvia Monticelli
In mammals, the 5'-methylcytosine (5mC) modification in the genomic DNA contributes to the dynamic control of gene expression. 5mC erasure is required for the activation of developmental programs and occurs either by passive dilution through DNA replication, or by enzymatic oxidation of the methyl mark to 5-hydroxymethylcytosine (5hmC), which can persist as such or undergo further oxidation and enzymatic removal. The relative contribution of each mechanism to epigenetic control in dynamic biological systems still remains a compelling question...
January 30, 2019: European Journal of Immunology
https://read.qxmd.com/read/30693981/alteration-of-the-tumour-suppressor-sardh-in-sporadic-colorectal-cancer-a-functional-and-transcriptome-profiling-based-study
#12
Hongjuan He, Erfei Chen, Lei Lei, Bianbian Yan, Xiaojuan Zhao, Ziqing Zhu, Qiqi Li, Pan Zhang, Wei Zhang, Jinliang Xing, Le Du, Jing Dong, Jin Yang
Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c.551C > T mutation in SARDH in sCRC. SARDH was identified as a novel tumour suppressor gene and was abnormally decreased in sCRC at both the transcriptional and the translational level...
January 29, 2019: Molecular Carcinogenesis
https://read.qxmd.com/read/30683020/the-bromodomain-and-extra-terminal-protein-inhibitor-otx015-suppresses-t-helper-cell-proliferation-and-differentiation
#13
Xiao Hu, Lauren P Schewitz-Bowers, Philippa J P Lait, David A Copland, Madeleine L Stimpson, Jing Jing Li, Yizhi Liu, Andrew D Dick, Richard W J Lee, Lai Wei
BACKGROUND: Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhibition. In this study we tested a new BET inhibitor under clinical development, OTX015, to interrogate its effects on key CD4+ T cell subsets associated with autoimmunity...
January 25, 2019: Current Molecular Medicine
https://read.qxmd.com/read/30681738/alpha-1-antitrypsin-deficiency-liver-disease-mutational-homogeneity-modulated-by-epigenetic-heterogeneity-with-links-to-obesity
#14
Liguo Wang, George W Marek, Ryan A Hlady, Ryan T Wagner, Xia Zhao, Virginia C Clark, Alex Xiucheng Fan, Chen Liu, Mark Brantly, Keith D Robertson
Alpha-1 Antitrypsin Deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in AATD patients. We examined the contribution of DNA methylation (5mC) to AATD liver disease heterogeneity since 5mC responds to environmental and genetic cues, and its deregulation is a major driver of liver disease...
January 25, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://read.qxmd.com/read/30674261/zinc-dependent-deacetylase-hdac-inhibitors-with-different-zbg-groups
#15
Yan Li, Fang Wang, Xiaoxue Chen, Jie Wang, Yonglong Zhao, Yongjun Li, Bin He
The state of histone acetylation plays a very crucial role in carcinogenesis and its development by chromatin remodeling and thus altering transcription of oncogenes and tumor suppressor genes. Such epigenetic regulation was controlled by zinc-dependent histone deacetylases (HDACs), one of major regulators. Due to the therapeutic potential of HDACs as one of promising drug targets in cancer, HDAC inhibitors have been intensively investigated over last few decades. Notably, there are five HDAC inhibitors already approved to the market...
January 22, 2019: Current Topics in Medicinal Chemistry
https://read.qxmd.com/read/30659025/epigenetic-silencing-affects-l-asparaginase-sensitivity-and-predicts-outcome-in-t-all
#16
Aurore Touzart, Etienne Lengline, Mehdi Latiri, Mohamed Belhocine, Charlotte Smith, Xavier Thomas, Salvatore Spicuglia, Denis Puthier, Françoise Pflumio, Thibaut Leguay, Carlos Graux, Yves Chalandon, Francoise Huguet, Stéphane Leprêtre, Norbert Ifrah, Hervé Dombret, Elizabeth Macintyre, Mathilde Hunault-Berger, Nicolas Boissel, Vahid Asnafi
PURPOSE: Biological explanations for discrepancies in patients related response to chemotherapy depending on the underlying oncogenic events is a promising research area. TLX1 or TLX3 deregulated T-ALLs (TLX1/3+) share an immature cortical phenotype and similar transcriptional signatures. However, their prognostic impacts differ and inconsistent clinical outcome has been reported for TLX3. We therefore hypothesized that the overlapping transcriptional profiles of TLX1+ and TLX3+ T-ALLs would allow identification of candidate genes which might determine their distinct clinical outcomes...
January 18, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://read.qxmd.com/read/30648438/a-comprehensive-catalog-of-lncrnas-expressed-in-t-cell-acute-lymphoblastic-leukemia
#17
Yasmina Kermezli, Wiam Saadi, Mohamed Belhocine, Eve-Lyne Mathieu, Marc-Antoine Garibal, Vahid Asnafi, Mourad Aribi, Salvatore Spicuglia, Denis Puthier
Several studies have demonstrated that LncRNAs can play major roles in cancer development. The creation of a catalog of LncRNAs expressed in T cell acute lymphoblastic leukemia (T-ALL) is thus of particular importance. However, this task is challenging as LncRNA expression is highly restricted in time and space manner and thus may greatly differ between samples. We performed a systematic transcript discovery in RNA-Seq data obtained from T-ALL primary cells and cell lines. This led to the identification of 2560 novel LncRNAs...
January 16, 2019: Leukemia & Lymphoma
https://read.qxmd.com/read/30637949/the-runx1-eto-fusion-protein-trans-activates-c-kit-expression-by-recruiting-histone-acetyltransferase-p300-on-its-promoter
#18
Guofeng Chen, Anqi Liu, Yihan Xu, Li Gao, Mengmeng Jiang, Yan Li, Na Lv, Lei Zhou, Lili Wang, Li Yu, Yonghui Li
The oncoprotein RUNX1-ETO is the fusion product of t(8;21)(q22;q22) and constitutes one of the most common genetic alterations in acute myeloid leukemia (AML). Abnormal c-KIT over-expression is considered an independent negative prognostic factor for relapse and survival in t(8;21) AML patients. However, the molecular mechanism of high c-KIT expression in t(8;21) AML remains unknown. In this study, we detected RUNX1-ETO and c-KIT gene expression in AML-M2 patients and verified the over-expression of c-KIT in t(8;21) AML patients...
January 13, 2019: FEBS Journal
https://read.qxmd.com/read/30637412/epigenetics-and-sphingolipid-metabolism-in-health-and-disease
#19
Weiyuan Wang, Paul T Toran, Rachel Sabol, Timothy J Brown, Brian M Barth
Sphingolipids represent one of the major classes of bioactive lipids. Studies of sphingolipids have intensified in the past several years, revealing their roles in nearly all cell biological processes. In addition, epigenetic regulation has gained substantial interest due to its role in controlling gene expression and activity without changing the genetic code. In this review, we first introduce a brief background on sphingolipid biology, highlighting its role in pathophysiology. We then illustrate the concept of epigenetic regulation, focusing on how it affects the metabolism of sphingolipids...
October 2018: International Journal of Biopharmaceutical Sciences
https://read.qxmd.com/read/30622680/new-findings-showing-how-dna-methylation-influences-diseases
#20
EDITORIAL
Fabio Sallustio, Loreto Gesualdo, Anna Gallone
In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells. Major differences have been found between differentiated cells and stem cells...
January 7, 2019: World Journal of Biological Chemistry
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