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https://www.readbyqxmd.com/read/28933623/the-defining-dna-methylation-signature-of-kabuki-syndrome-enables-functional-assessment-of-genetic-variants-of-unknown-clinical-significance
#1
Erfan Aref-Eshghi, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, David Rodenhiser, Charles Schwartz, Bekim Sadikovic
Kabuki syndrome (KS) is caused by mutations in KMT2D, which is a histone methyltransferase involved in methylation of H3K4, a histone marker associated with DNA methylation. Analysis of >450,000 CpGs in 24 KS patients with pathogenic mutations in KMT2D and 216 controls, identified several genomic regions, along with 1,504 CpG sites with significant DNA methylation changes including a number of Hox genes and the MYO1F gene. Using the most differentiating and significant probes and regions we developed a "methylation variant pathogenicity (MVP) score," which enables 100% sensitive and specific identification of individuals with KS, which was confirmed using multiple public and internal patient DNA methylation databases...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28932414/hox-gene-cluster-of-the-ascidian-halocynthia-roretzi-reveals-multiple-ancient-steps-of-cluster-disintegration-during-ascidian-evolution
#2
Yuka Sekigami, Takuya Kobayashi, Ai Omi, Koki Nishitsuji, Tetsuro Ikuta, Asao Fujiyama, Noriyuki Satoh, Hidetoshi Saiga
BACKGROUND: Hox gene clusters with at least 13 paralog group (PG) members are common in vertebrate genomes and in that of amphioxus. Ascidians, which belong to the subphylum Tunicata (Urochordata), are phylogenetically positioned between vertebrates and amphioxus, and traditionally divided into two groups: the Pleurogona and the Enterogona. An enterogonan ascidian, Ciona intestinalis (Ci), possesses nine Hox genes localized on two chromosomes; thus, the Hox gene cluster is disintegrated...
2017: Zoological Letters
https://www.readbyqxmd.com/read/28931862/long-non-coding-rna-hotair-promotes-cell-migration-by-upregulating-insulin-growth-factor-binding-protein-2-in-renal-cell-carcinoma
#3
Hiromichi Katayama, Keiichi Tamai, Rie Shibuya, Mao Nakamura, Mai Mochizuki, Kazunori Yamaguchi, Sadafumi Kawamura, Tatsuo Tochigi, Ikuro Sato, Takamasa Okanishi, Kunie Sakurai, Wataru Fujibuchi, Yoichi Arai, Kennichi Satoh
Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28927461/additional-sex-combs-interacts-with-enhancer-of-zeste-and-trithorax-and-modulates-levels-of-trimethylation-on-histone-h3k4-and-h3k27-during-transcription-of-hsp70
#4
Taosui Li, Jacob W Hodgson, Svetlana Petruk, Alexander Mazo, Hugh W Brock
BACKGROUND: Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. RESULTS: We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues...
September 19, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28919500/hydrogen-and-oxygen-trapping-at-the-h-cluster-of-fefe-%C3%A2-hydrogenase-revealed-by-site-selective-spectroscopy-and-qm-mm-calculations
#5
Stefan Mebs, Ramona Kositzki, Jifu Duan, Moritz Senger, Florian Wittkamp, Ulf-Peter Apfel, Thomas Happe, Sven T Stripp, Martin Winkler, Michael Haumann
[FeFe]‑hydrogenases are superior hydrogen conversion catalysts. They bind a cofactor (H-cluster) comprising a four‑iron and a diiron unit with three carbon monoxide (CO) and two cyanide (CN(-)) ligands. Hydrogen (H2) and oxygen (O2) binding at the H-cluster was studied in the C169A variant of [FeFe]‑hydrogenase HYDA1, in comparison to the active oxidized (Hox) and CO-inhibited (Hox-CO) species in wildtype enzyme. (57)Fe labeling of the diiron site was achieved by in vitro maturation with a synthetic cofactor analogue...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28919208/genetics-of-clubfoot-recent-progress-and-future-perspectives
#6
REVIEW
Sulman Basit, Khalid I Khoshhal
Clubfoot or talipes equinovarus (TEV) is an inborn three-dimensional deformity of leg, ankle and foot. It results from structural defects of several tissues of foot and lower leg leading to abnormal positioning of foot and ankle joints. TEV can lead to long-lasting functional disability, malformation and discomfort if left untreated. Substantial progress has been achieved in the management and diagnosis of limb defects; however, not much is known about the molecular players and signalling pathways underlying TEV disorder...
September 14, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28914367/no-association-of-single-nucleotide-polymorphisms-within-h19-and-hox-transcript-antisense-rna-hotair-with-genetic-susceptibility-to-systemic-lupus-erythematosus-rheumatoid-arthritis-and-primary-sj%C3%A3-gren-s-syndrome-in-a-chinese-han-population
#7
An-Fang Huang, Lin-Chong Su, Hong Jia, Yi Liu, Wang-Dong Xu
The H19 (rs2839698, rs3741219) and HOTAIR (rs920778) polymorphisms were related to many kinds of cancers. However, these polymorphisms have been scarcely explored in different autoimmune diseases. Here, we aimed to examine the association of the polymorphisms with susceptibility to or protection against systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS) among Chinese Han patients. We conducted a case-control study including 800 patients (300 with SLE, 350 with RA, and 150 with pSS) and 350 healthy control individuals...
September 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28913932/hox-d-genes-and-the-fin-to-limb-transition-insights-from-fish-studies
#8
REVIEW
Ana Paço, Renata Freitas
Genes in the 5' extremity of the HoxD cluster encode DNA-binding transcription factors essential for development of the autopod and digits, regulating primarily gene expression and, consequently, morphogenesis and skeletal differentiation. Comparative studies focused on their expression and regulation have led to the idea that evolution of a bimodal regulation of the HoxD cluster, mainly due to the activation of cis-regulatory units in the centromeric side of the cluster, was a fundamental mechanism that potentiated the fin-to-limb transition in vertebrates...
September 14, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28912427/dna-methylation-profiling-reveals-common-signatures-of-tumorigenesis-and-defines-epigenetic-prognostic-subtypes-of-canine-diffuse-large-b-cell-lymphoma
#9
Serena Ferraresso, Arianna Aricò, Tiziana Sanavia, Silvia Da Ros, Massimo Milan, Luciano Cascione, Stefano Comazzi, Valeria Martini, Mery Giantin, Barbara Di Camillo, Sandro Mazzariol, Diana Giannuzzi, Laura Marconato, Luca Aresu
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912272/the-transcription-factor-hoxb7-regulates-erk-kinase-activity-and-thereby-stimulates-the-motility-and-invasiveness-of-pancreatic-cancer-cells
#10
Makiko Tsuboi, Keisuke Taniuchi, Takahiro Shimizu, Motoaki Saito, Toshiji Saibara
HOX genes encode transcription factors that function as sequence-specific transcription factors that are involved in cellular proliferation, differentiation, and death. The aim of this study was to investigate the role of a HOX family protein, HOXB7, in the motility and invasiveness of pancreatic cancer cells. We previously identified a HOXB7 transcript that is one of a number of transcripts that are preferentially translated in membrane protrusions in pancreatic cancer cells. Immunocytochemistry showed that HOXB7 was localized to the cell protrusions of migrating pancreatic cancer cells...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28887733/computational-design-of-bio-inspired-carnosine-based-hobr-antioxidants
#11
Farzaneh Sarrami, Li-Juan Yu, Amir Karton
During a respiratory burst the enzyme myeloperoxidase generates significant amounts of hypohalous acids (HOX, X = Cl and Br) in order to inflict oxidative damage upon invading pathogens. However, excessive production of these potent oxidants is associated with numerous inflammatory diseases. It has been suggested that the endogenous antioxidant carnosine is an effective HOCl scavenger. Recent computational and experimental studies suggested that an intramolecular Cl(+) transfer from the imidazole ring to the terminal amine might play an important role in the antioxidant activity of carnosine...
September 8, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28885616/myd88-is-an-essential-component-of-retinoic-acid-induced-differentiation-in-human-pluripotent-embryonal-carcinoma-cells
#12
Gomaa Sulaiman, Aoife Cooke, Brendan Ffrench, Claudia Gasch, Olayemi Azeez Abdullai, Kevin O'Connor, Salah Elbaruni, Gordon Blackshields, Cathy Spillane, Helen Keegan, Victoria McEneaney, Ronan Knittel, Annamarie Rogers, Ian B Jeffery, Brendan Doyle, Mark Bates, Charles d'Adhemar, Mathia Yc Lee, Eric L Campbell, Paul N Moynagh, Desmond G Higgins, Sharon O'Toole, Luke O'Neill, John J O'Leary, Michael F Gallagher
We have previously reported that myeloid differentiation primary response gene 88 (MyD88) is downregulated during all-trans retinoic acid (RA)-induced differentiation of pluripotent NTera2 human embryonal carcinoma cells (hECCs), whereas its maintained expression is associated with RA differentiation resistance in nullipotent 2102Ep hECCs. MyD88 is the main adapter for toll-like receptor (TLR) signalling, where it determines the secretion of chemokines and cytokines in response to pathogens. In this study, we report that loss of MyD88 is essential for RA-facilitated differentiation of hECCs...
September 8, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28884175/protonation-reduction-dynamics-at-the-4fe-4s-cluster-of-the-hydrogen-forming-cofactor-in-fefe-hydrogenases
#13
Moritz Senger, Stefan Mebs, Jifu Duan, Olga Shulenina, Konstantin Laun, Leonie Kertess, Florian Wittkamp, Ulf-Peter Apfel, Thomas Happe, Martin Winkler, Michael Haumann, Sven T Stripp
The [FeFe]-hydrogenases of bacteria and algae are the most efficient hydrogen conversion catalysts in nature. Their active-site cofactor (H-cluster) comprises a [4Fe-4S] cluster linked to a unique diiron site that binds three carbon monoxide (CO) and two cyanide (CN(-)) ligands. Understanding microbial hydrogen conversion requires elucidation of the interplay of proton and electron transfer events at the H-cluster. We performed real-time spectroscopy on [FeFe]-hydrogenase protein films under controlled variation of atmospheric gas composition, sample pH, and reductant concentration...
September 8, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28877686/disease-stabilizing-treatment-based-on-all-trans-retinoic-acid-and-valproic-acid-in-acute-myeloid-leukemia-identification-of-responders-by-gene-expression-profiling-of-pretreatment-leukemic-cells
#14
Håkon Reikvam, Randi Hovland, Rakel Brendsdal Forthun, Sigrid Erdal, Bjørn Tore Gjertsen, Hanne Fredly, Øystein Bruserud
BACKGROUND: Acute myeloid leukemia (AML) is an aggressive malignancy only cured by intensive therapy. However, many elderly and unfit patients cannot receive such treatment due to an unacceptable risk of treatment-related morbidity and mortality. Disease-stabilizing therapy is then the only possible strategy, one alternative being treatment based on all-trans retinoic acid (ATRA) combined with the histone deacetylase inhibitor valproic acid and possibly low-toxicity conventional chemotherapy...
September 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28875454/roles-of-retinoic-acid-signaling-in-shaping-the-neuronal-architecture-of-the-developing-amphioxus-nervous-system
#15
Elisabeth Zieger, Simona Candiani, Greta Garbarino, Jenifer C Croce, Michael Schubert
The morphogen retinoic acid (RA) patterns vertebrate nervous systems and drives neurogenesis, but how these functions evolved remains elusive. Here, we show that RA signaling plays stage- and tissue-specific roles during the formation of neural cell populations with serotonin, dopamine, and GABA neurotransmitter phenotypes in amphioxus, a proxy for the ancestral chordate. Our data suggest that RA signaling restricts the specification of dopamine-containing cells in the ectoderm and of GABA neurons in the neural tube, probably by regulating Hox1 and Hox3 gene expression, respectively...
September 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28871058/the-hox-proteins-ubx-and-abda-collaborate-with-the-transcription-pausing-factor-m1bp-to-regulate-gene-transcription
#16
Amel Zouaz, Ankush Auradkar, Marie Claire Delfini, Meiggie Macchi, Marine Barthez, Serge Ela Akoa, Leila Bastianelli, Gengqiang Xie, Wu-Min Deng, Stuart S Levine, Yacine Graba, Andrew J Saurin
In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Drosophila Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter-proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature...
September 4, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28860158/embryonic-timing-axial-stem-cells-chromatin-dynamics-and-the-hox-clock
#17
REVIEW
Jacqueline Deschamps, Denis Duboule
Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with large-scale regulation and chromatin structure during the development of both axial and limb patterns. We further discuss how this sequential transcriptional activation marks embryonic stem cell-like axial progenitors in mammals and, consequently, how a temporal genetic system is further translated into spatial coordinates via the fate of these progenitors...
July 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28857242/down-regulation-of-the-long-noncoding-rna-hox-transcript-antisense-intergenic-rna-inhibits-the-occurrence-and-progression-of-glioma
#18
Bin Yang, Zhen-Yu Wei, Bang-Qing Wang, Hua-Chao Yang, Jun-Yi Wang, Xing-Yao Bu
This study aims to explore the role of long noncoding RNA (lncRNA)-HOX transcript antisense intergenic RNA (HOTAIR) in the occurrence and progression of glioma. Fresh glioma and normal brain tissues were classified into a glioma group (n = 67) and a normal group (n = 64) respectively. U87 cells were assigned into the blank, sh-NC and sh-HOTAIR groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine HOTAIR expression. Cell proliferation, cell cycle and cell apoptosis rates were detected by cell counting kit-8 (CCK-8) and flow cytometry (FCM)...
August 31, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28855339/role-of-remodeling-and-spacing-factor-1-in-histone-h2a-ubiquitination-mediated-gene-silencing
#19
Zhuo Zhang, Amanda E Jones, Wei Wu, Jinman Kim, Yue Kang, Xiaobao Bi, Yue Gu, Ivan K Popov, Matthew B Renfrow, Marina N Vassylyeva, Dmitry G Vassylyev, Keith E Giles, Dongquan Chen, Ashwath Kumar, Yuhong Fan, Yufeng Tong, Chuan-Fa Liu, Woojin An, Chenbei Chang, Jianjun Luo, Louise T Chow, Hengbin Wang
Posttranslational histone modifications play important roles in regulating chromatin-based nuclear processes. Histone H2AK119 ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing. However, the underlying mechanism remains largely obscure. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF complex, as a H2Aub binding protein, which mediates the gene-silencing function of this histone modification. RSF1 associates specifically with H2Aub, but not H2Bub nucleosomes, through a previously uncharacterized and obligatory region designated as ubiquitinated H2A binding domain...
August 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28851216/activation-thermodynamics-and-h-d-kinetic-isotope-effect-of-the-hox-to-hredh-transition-in-fefe-hydrogenase
#20
Michael W Ratzloff, Molly B Wilker, David W Mulder, Carolyn E Lubner, Hayden Hamby, Katherine A Brown, Gordana Dukovic, Paul W King
Molecular complexes between CdSe nanocrystals and Clostridium acetobutylicum [FeFe] hydrogenase I (CaI) enabled light-driven control of electron transfer for spectroscopic detection of redox intermediates during catalytic proton reduction. Here we address the route of electron transfer from CdSe→CaI and activation thermodynamics of the initial step of proton reduction in CaI. The electron paramagnetic spectroscopy of illuminated CdSe:CaI showed how the CaI accessory FeS cluster chain (F-clusters) functions in electron transfer with CdSe...
September 6, 2017: Journal of the American Chemical Society
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