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https://www.readbyqxmd.com/read/29141232/foxp1-promotes-embryonic-neural-stem-cell-differentiation-by-repressing-jagged1-expression
#1
Luca Braccioli, Stephin J Vervoort, Youri Adolfs, Cobi J Heijnen, Onur Basak, R Jeroen Pasterkamp, Cora H Nijboer, Paul J Coffer
Mutations in FOXP1 have been linked to neurodevelopmental disorders including intellectual disability and autism; however, the underlying molecular mechanisms remain ill-defined. Here, we demonstrate with RNA and chromatin immunoprecipitation sequencing that FOXP1 directly regulates genes controlling neurogenesis. We show that FOXP1 is expressed in embryonic neural stem cells (NSCs), and modulation of FOXP1 expression affects both neuron and astrocyte differentiation. Using a murine model of cortical development, FOXP1-knockdown in utero was found to reduce NSC differentiation and migration during corticogenesis...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29141224/genetic-and-genomic-characterization-of-462-melanoma-patient-derived-xenografts-tumor-biopsies-and-cell-lines
#2
Bradley Garman, Ioannis N Anastopoulos, Clemens Krepler, Patricia Brafford, Katrin Sproesser, Yuchao Jiang, Bradley Wubbenhorst, Ravi Amaravadi, Joseph Bennett, Marilda Beqiri, David Elder, Keith T Flaherty, Dennie T Frederick, Tara C Gangadhar, Michael Guarino, David Hoon, Giorgos Karakousis, Qin Liu, Nandita Mitra, Nicholas J Petrelli, Lynn Schuchter, Batool Shannan, Carol L Shields, Jennifer Wargo, Brandon Wenz, Melissa A Wilson, Min Xiao, Wei Xu, Xaiowei Xu, Xiangfan Yin, Nancy R Zhang, Michael A Davies, Meenhard Herlyn, Katherine L Nathanson
Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140466/transcription-induced-supercoiling-as-the-driving-force-of-chromatin-loop-extrusion-during-formation-of-tads-in-interphase-chromosomes
#3
Dusan Racko, Fabrizio Benedetti, Julien Dorier, Andrzej Stasiak
Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders...
November 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29138836/gata4-protects-against-hyperglycemia%C3%A2-induced-endothelial-dysfunction-by-regulating-nox4-transcription
#4
Hongfei Xu, Zhen Wang, Zewei Sun, Yiming Ni, Liangrong Zheng
Endothelial dysfunction is one of the most common complications associated with diabetes and may lead to atherosclerosis. Conflicting reports indicate that NADPH oxidase 4 (NOX4) induces hydrogen peroxide production and cytotoxicity, but also has a protective effect on endothelial dysfunction. The present study aimed to identify the transcription factor responsible for NOX4 expression using a transcription factor activation profiling plate array and chromatin immunoprecipitation. Data from these analyses indicated that GATA‑binding protein 4 (GATA4) was able to mediate NOX4 transcription and is downregulated in human umbilical vein endothelial cells (HUVECs) that were exposed to hyperglycemic conditions as well as in the endothelial cells of a mouse diabetes model...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138824/genetic-mutational-testing-of-chinese-children-with-familial-hematuria-with-biopsy%C3%A2-proven-fsgs
#5
Yongzhen Li, Ying Wang, Qingnan He, Xiqiang Dang, Yan Cao, Xiaochuan Wu, Shuanghong Mo, Xiaoxie He, Zhuwen Yi
Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH)...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138751/expression-of-microrna-29a-regulated-by-yes-associated-protein-modulates-the-neurite-outgrowth-in-n2a-cells
#6
Chunye Tan, Changlin Yu, Zhiwen Song, Hongjun Zou, Xu Xu, Jinbo Liu
Yes-associated protein (YAP) is proved to increase miR-29a in the present study, but the relevant molecular mechanism is not clear. Also, growing evidence indicates that the high-level miR-29a promotes the neurite outgrowth by decreasing PTEN (phosphatase and tensin homologue deleted on chromosome 10). Results show that the expression of miR-29a increases but the PTEN decreases during transfecting the N2a cells with the YAP plasmid. Meanwhile, the advancement of neurite outgrowth is presented via using multiple methods to detect the expression of GAP-43 and NF-200, which have a strong association with neurite outgrowth...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29138516/the-functions-and-unique-features-of-long-intergenic-non-coding-rna
#7
REVIEW
Julia D Ransohoff, Yuning Wei, Paul A Khavari
Long intergenic non-coding RNA (lincRNA) genes have diverse features that distinguish them from mRNA-encoding genes and exercise functions such as remodelling chromatin and genome architecture, RNA stabilization and transcription regulation, including enhancer-associated activity. Some genes currently annotated as encoding lincRNAs include small open reading frames (smORFs) and encode functional peptides and thus may be more properly classified as coding RNAs. lincRNAs may broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity through a diversity of mechanisms, highlighting our rapidly evolving understanding of the non-coding genome...
November 15, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29138512/proteome-wide-identification-of-lysine-2-hydroxyisobutyrylation-reveals-conserved-and-novel-histone-modifications-in-physcomitrella-patens
#8
Zhiming Yu, Jun Ni, Wei Sheng, Zhikun Wang, Yuhuan Wu
Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly identified post-translational modification found in animal and yeast cells. Previous research suggested that histone Khib is involved in male cell differentiation and plays a critical role in the regulation of chromatin functions in animals. However, information regarding protein Khib in plants is still limited. In this study, using a specific antibody and LC-MS/MS methods, we identified 11,976 Khib sites in 3,001 proteins in Physcomitrella patens. The bioinformatics analysis indicated that these Khib-modified proteins were involved in a wide range of molecular functions and cellular processes, and showed diverse subcellular localizations...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138493/suppression-of-srcap-chromatin-remodelling-complex-and-restriction-of-lymphoid-lineage-commitment-by-pcid2
#9
Buqing Ye, Benyu Liu, Liuliu Yang, Guanling Huang, Lu Hao, Pengyan Xia, Shuo Wang, Ying Du, Xiwen Qin, Pingping Zhu, Jiayi Wu, Nobuo Sakaguchi, Junyan Zhang, Zusen Fan
Lymphoid lineage commitment is an important process in haematopoiesis, which forms the immune system to protect the host from pathogen invasion. However, how multipotent progenitors (MPP) switch into common lymphoid progenitors (CLP) or common myeloid progenitors (CMP) during this process remains elusive. Here we show that PCI domain-containing protein 2 (Pcid2) is highly expressed in MPPs. Pcid2 deletion in the haematopoietic system causes skewed lymphoid lineage specification. In MPPs, Pcid2 interacts with the Zinc finger HIT-type containing 1 (ZNHIT1) to block Snf2-related CREBBP activator protein (SRCAP) activity and prevents the deposition of histone variant H2A...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29138400/accessibility-of-the-histone-h3-tail-in-the-nucleosome-for-binding-of-paired-readers
#10
Jovylyn Gatchalian, Xiaodong Wang, Jinzen Ikebe, Khan L Cox, Adam H Tencer, Yi Zhang, Nathaniel L Burge, Luo Di, Matthew D Gibson, Catherine A Musselman, Michael G Poirier, Hidetoshi Kono, Jeffrey J Hayes, Tatiana G Kutateladze
Combinatorial polyvalent contacts of histone-binding domains or readers commonly mediate localization and activities of chromatin-associated proteins. A pair of readers, the PHD fingers of the protein CHD4, has been shown to bivalently recognize histone H3 tails. Here we describe a mechanism by which these linked but independent readers bind to the intact nucleosome core particle (NCP). Comprehensive NMR, chemical reactivity, molecular dynamics, and fluorescence analyses point to the critical roles of intra-nucleosomal histone-DNA interactions that reduce the accessibility of H3 tails in NCP, the nucleosomal DNA, and the linker between readers in modulating nucleosome- and/or histone-binding activities of the readers...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29138238/a-resource-for-the-allele-specific-analysis-of-dna-methylation-at-multiple-genomically-imprinted-loci-in-mice
#11
Jadiel A Wasson, Onur Birol, David J Katz
Genomically imprinted loci are expressed mono-allelically dependent upon the parent of origin. Their regulation not only illuminates how chromatin regulates gene expression but also how chromatin can be reprogrammed every generation. Because of their distinct parent of origin regulation, analysis of imprinted loci can be difficult. Single nucleotide polymorphisms (SNPs) are required to accurately assess these elements allele-specifically. However, publicly available SNP databases lack robust verification, making analysis of imprinting difficult...
November 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29137925/polycomb-repression-complex-2-is-required-for-the-maintenance-of-retinal-progenitor-cells-and-balanced-retinal-differentiation
#12
Naoko Fujimura, Andrea Kuzelova, Anja Ebert, Hynek Strnad, Jitka Lachova, Ondrej Machon, Meinrad Busslinger, Zbynek Kozmik
Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Müller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage...
November 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29137603/clustertad-an-unsupervised-machine-learning-approach-to-detecting-topologically-associated-domains-of-chromosomes-from-hi-c-data
#13
Oluwatosin Oluwadare, Jianlin Cheng
BACKGROUND: With the development of chromosomal conformation capturing techniques, particularly, the Hi-C technique, the study of the spatial conformation of a genome is becoming an important topic in bioinformatics and computational biology. The Hi-C technique can generate genome-wide chromosomal interaction (contact) data, which can be used to investigate the higher-level organization of chromosomes, such as Topologically Associated Domains (TAD), i.e., locally packed chromosome regions bounded together by intra chromosomal contacts...
November 14, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29137412/long-non-coding-rna-snhg15-inhibits-p15-and-klf2-expression-to-promote-pancreatic-cancer-proliferation-through-ezh2-mediated-h3k27me3
#14
Zhonghua Ma, Hesuyuan Huang, Jirong Wang, Yan Zhou, Fuxing Pu, Qinghong Zhao, Peng Peng, Bingqing Hui, Hao Ji, Keming Wang
Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137255/potential-genotoxic-and-cytotoxicity-of-emamectin-benzoate-in-human-normal-liver-cells
#15
Zhijie Zhang, Xinyu Zhao, Xiaosong Qin
Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#16
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136510/genomic-subtypes-of-non-invasive-bladder-cancer-with-distinct-metabolic-profile-and-female-gender-bias-in-kdm6a-mutation-frequency
#17
Carolyn D Hurst, Olivia Alder, Fiona M Platt, Alastair Droop, Lucy F Stead, Julie E Burns, George J Burghel, Sunjay Jain, Leszek J Klimczak, Helen Lindsay, Jo-An Roulson, Claire F Taylor, Helene Thygesen, Angus J Cameron, Anne J Ridley, Helen R Mott, Dmitry A Gordenin, Margaret A Knowles
Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136504/arid1a-has-context-dependent-oncogenic-and-tumor-suppressor-functions-in-liver-cancer
#18
Xuxu Sun, Sam C Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C Yopp, Amit G Singal, Hao Zhu
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be tumor suppressive. In some hepatocellular carcinoma patients, ARID1A was highly expressed in primary tumors but not in metastatic lesions, suggesting that ARID1A can be lost after initiation. Mice with liver-specific homozygous or heterozygous Arid1a loss were resistant to tumor initiation while ARID1A overexpression accelerated initiation. In contrast, homozygous or heterozygous Arid1a loss in established tumors accelerated progression and metastasis...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29135156/-isolated-teratozoospermia-is-there-a-role-for-antioxidant-therapy
#19
E A Efremov, E V Kasatonova, Ya I Melnik, A A Nikushina
Recently, literature has emerged that offers contradictory findings of idiopathic forms of isolated teratozoospermia that may confuse clinicians. Some researchers argue that at 0-1% of normal forms of spermatozoa, morphology itself cannot be a prognostic indicator of fertility, either in the planning of natural pregnancy, or when used in assisted reproduction. In this connection, the possible causes of teratozoospermia and alternative therapies are being actively sought, in addition to known invasive and costly procedures...
October 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/29134711/x-exceptionalism-in-caenorhabditis-speciation
#20
Asher D Cutter
Speciation genetics research in diverse organisms shows the X-chromosome to be exceptional in how it contributes to 'rules' of speciation. Until recently, however, the nematode phylum has been nearly silent on this issue, despite the model organism Caenorhabditis elegans having touched most other topics in biology. Studies of speciation with Caenorhabditis accelerated with the recent discovery of species pairs showing partial inter-fertility. The resulting genetic analyses of reproductive isolation in nematodes demonstrate key roles for the X-chromosome in hybrid male sterility and inviability, opening up new understanding of the genetic causes of Haldane's rule, Darwin's corollary to Haldane's rule, and enabling tests of the large-X effect hypothesis...
November 13, 2017: Molecular Ecology
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