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https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#1
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934506/clip-seq-analysis-of-multi-mapped-reads-discovers-novel-functional-rna-regulatory-sites-in-the-human-transcriptome
#2
Zijun Zhang, Yi Xing
Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933854/epigenetic-dna-modification-n6-methyladenine-causes-site-specific-rna-polymerase-ii-transcriptional-pausing
#3
Wei Wang, Liang Xu, Lulu Hu, Jenny Chong, Chuan He, Dong Wang
N6-methyladenine (N6-mA or 6mA) is an epigenetic DNA modification in eukaryotic genomes. In contrast to the well-established roles of 5-methylcytosine for epigenetic regulation of gene expression, the functional roles of N6-mA remain elusive. In particular, the impact of N6-mA modification at DNA template on RNA polymerase II (pol II) transcription elongation is not known. In this work, using the Saccharomyces cerevisiae pol II transcriptional elongation system as a model, we investigated the molecular mechanism of pol II recognition and processing of N6-mA sites via both biochemical and structural approaches...
September 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28932910/a-histone-deacetylase-gene-slhda3-acts-as-a-negative-regulator-of-fruit-ripening-and-carotenoid-accumulation
#4
Jun-E Guo, Zongli Hu, Xiaohui Yu, Anzhou Li, Fenfen Li, Yunshu Wang, Shibing Tian, Guoping Chen
SlHDA3 functions as an inhibitor and regulates tomato fruit ripening and carotenoid accumulation. Post-translational modifications, including histones acetylation, play a pivotal role in the changes of chromatin structure dynamic modulation and gene activity. The regulation of histone acetylation is achieved by the action of histone acetyltransferases and deacetylases, which play crucial roles in the regulation of transcription activation. There is an increasing research focus on histone deacetylation in crops, but the role of histone deacetylase genes (HDACs) in tomato has not been elucidated...
September 20, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28932198/progress-and-prospects-of-crispr-cas-systems-in-insects-and-other-arthropods
#5
REVIEW
Dan Sun, Zhaojiang Guo, Yong Liu, Youjun Zhang
Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated gene Cas9 represent an invaluable system for the precise editing of genes in diverse species. The CRISPR/Cas9 system is an adaptive mechanism that enables bacteria and archaeal species to resist invading viruses and phages or plasmids. Compared with zinc finger nucleases and transcription activator-like effector nucleases, the CRISPR/Cas9 system has the advantage of requiring less time and effort. This efficient technology has been used in many species, including diverse arthropods that are relevant to agriculture, forestry, fisheries, and public health; however, there is no review that systematically summarizes its successful application in the editing of both insect and non-insect arthropod genomes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28931541/molecular-mechanisms-involved-in-the-adaptive-regulation-of-colonic-thiamin-pyrophosphate-tpp-uptake-process
#6
Kasin Yadunandam Anandam, Padmanabhan Srinivasan, Veedamali S Subramanian, Hamid M Said
A considerable amount of the thiamin generated by gut microbiota exists in the form of thiamin pyrophosphate (TPP). We have previously shown that human colonocytes possess an efficient carrier-mediated uptake process for TPP that involves the SLC44A4 system and this uptake process is adaptively-regulated by prevailing extracellular TPP level. Little is known about the molecular mechanisms that mediate this adaptive regulation. We addressed this issue using human-derived colonic epithelial NCM460 cells and mouse colonoids as models...
September 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28930539/transcriptional-regulation-of-p57-kip2-expression-during-development-differentiation-and-disease
#7
Marianna N Rossi, Oriella Andresini, Francesca Matteini, Rossella Maione
p57(kip2) is the most complex member of the CIP/KIP family of cyclin-dependent kinase inhibitors and plays a fundamental role in regulating cell cycle and differentiation during mammalian development. Consistently with a key role for p57(kip2) in the spatial and temporal control of cell proliferation, its expression is fine-tuned by multiple regulatory mechanisms, resulting in a tissue-, developmental phase- and cell type-specific pattern. Moreover, p57(kip2) is an imprinted gene, further supporting the importance of its proper expression dosage...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930534/regulation-of-poly-adp-ribose-polymerase-1-functions-by-post-translational-modifications
#8
Lianhua Piao, Kyoko Fujioka, Makoto Nakakido, Ryuji Hamamoto
The poly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribosyl)ation, a post-translational modification of proteins. This  consists of the attachment of mono- or poly-adenosine diphosphate (ADP)-ribose units from nicotinamide adenine dinucleotide (NAD(+)) to specific polar residues of target proteins. PARP1 is the most abundant and best-characterized member of the family of PARP enzymes. PARP1 plays key roles in DNA repair, as well as a wide variety of cellular processes, including transcriptional regulation, chromatin modulation, cellular signaling pathway, inflammation, cellular stress responses and so on...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929346/o-glcnac-dependent-regulation-of-progesterone-receptor-function-in-breast-cancer
#9
Gloria M Trinca, Merit L Goodman, Evangelia K Papachristou, Clive S D'Santos, Prabhakar Chalise, Rashna Madan, Chad Slawson, Christy R Hagan
Emerging clinical trial data implicate progestins in the development of breast cancer. While the role for the progesterone receptor (PR) in this process remains controversial, it is clear that PR, a steroid-activated nuclear receptor, alters the transcriptional landscape of breast cancer. PR interacts with many different types of proteins, including transcriptional co-activators and co-repressors, transcription factors, nuclear receptors, and proteins that post-translationally modify PR (i.e., kinases and phosphatases)...
September 19, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28928876/heterochromatin-reduction-correlates-with-the-increase-of-the-kdm4b-and-kdm6a-demethylases-and-the-expression-of-pericentromeric-dna-during-the-acquisition-of-a-transformed-phenotype
#10
Cinthya Gurrion, Maritere Uriostegui, Mario Zurita
Cancer cells have alterations in chromatin organization, mostly a reduction in heterochromatin. How this process occurs during transformation and if it participates in the maintenance of a cancerous phenotype is not well understood. Here, using a transformation-inducible cell line, we analyzed the changes that occur in heterochromatin during transformation to a cancerous phenotype. After transformation, there is a reduction in heterochromatin bodies and a nuclear reorganization of HP1α. These occurrences correlate with reductions in H3K9me3 and H3K27me3 levels and with some of the enzymes that introduce these modifications...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928088/20-s-ginsenoside-rh2-suppresses-proliferation-and-migration-of-hepatocellular-carcinoma-cells-by-targeting-ezh2-to-regulate-cdkn2a-2b-gene-cluster-transcription
#11
Qi Li, Bai Li, Chengya Dong, Yajie Wang, Qi Li
20(S)-Ginsenoside Rh2 (20(S)-GRh2) exerts important pharmacological effects with regard to the control of human hepatocellular carcinoma (HCC). EZH2 is a potent histone methyltransferase of H3K27me(3), which has been determined as an oncogene in many malignancies. The CDKN2A-2B gene cluster encodes three important tumor suppressors, P14, P15 and P16. In this study, the anticancer effect and molecular mechanism of 20(S)-GRh2 on HCC was investigated. Treatment of HCC cells with 20(S)-GRh2 inhibited cell proliferation, migration and induced cell cycle arrest at the G0/G1 phase, and inhibited tumor growth in vivo...
September 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28927261/hdac11-inhibits-myoblast-differentiation-through-repression-of-myod-dependent-transcription
#12
Sang Kyung Byun, Tae Hyeon An, Min Jeong Son, Da Som Lee, Hyun Sup Kang, Eun-Woo Lee, Baek Soo Han, Won Kon Kim, Kwang-Hee Bae, Kyoung-Jin Oh, Sang Chul Lee
Abnormal differentiation of muscle is closely associated with aging (sarcopenia) and diseases such as cancer and type II diabetes. Thus, understanding the mechanisms that regulate muscle differentiation will be useful in the treatment and prevention of these conditions. Protein lysine acetylation and methylation are major post-translational modification mechanisms that regulate key cellular processes. In this study, to elucidate the relationship between myogenic differentiation and protein lysine acetylation/methylation, we performed a PCR array of enzymes related to protein lysine acetylation/ methylation during C2C12 myoblast differentiation...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28926586/sox14-activates-the-p53-signaling-pathway-and-induces-apoptosis-in-a-cervical-carcinoma-cell-line
#13
Danijela Stanisavljevic, Isidora Petrovic, Vladanka Vukovic, Marija Schwirtlich, Marija Gredic, Milena Stevanovic, Jelena Popovic
SOX14 is a member of the SOX family of transcription factors mainly involved in the regulation of neural development. Recently, it became evident that SOX14 is one of four hypermethylated genes in cervical carcinoma, considered as a tumor suppressor candidate in this type of malignancy. In this paper we elucidated the role of SOX14 in the regulation of malignant properties of cervical carcinoma cells in vitro. Functional analysis performed in HeLa cells revealed that SOX14 overexpression decreased viability and promoted apoptosis through altering the expression of apoptosis related genes...
2017: PloS One
https://www.readbyqxmd.com/read/28926431/epigenetic-regulation-of-dendritic-cell-development-and-function
#14
Yuanyuan Tian, Lijun Meng, Yi Zhang
The immune system is characterized by the generation of structurally and functionally heterogeneous immune cells that constitute complex innate and adaptive immunity. This heterogeneity of immune cells results from changes in the expression of genes without altering DNA sequence. To achieve this heterogeneity, immune cells orchestrate the expression and functional status of transcription factor (TF) networks, which can be broadly categorized into 3 classes: pioneer TFs that facilitate initial commitment and differentiation of hematopoietic cells, subset-specific TFs that promote the generation of selected cell lineages, and immune-signaling TFs that regulate specialized function in differentiated cells...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926429/targeting-histone-acetylation-readers-and-writers-in-leukemia-and-cancer
#15
Christopher B Benton, Warren Fiskus, Kapil N Bhalla
Chromatin packaging of DNA provides a framework for transcriptional regulation. Modifications to DNA and histone proteins in nucleosomes lead to conformational changes, alterations in the recruitment of transcriptional complexes, and ultimately modulation of gene expression. We provide a focused review of control mechanisms that help modulate the activation and deactivation of gene transcription specifically through histone acetylation writers and readers in cancer. The chemistry of these modifications is subject to clinically actionable targeting, including state-of-the-art strategies to inhibit basic oncogenic mechanisms related to histone acetylation...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926184/experience-dependent-neural-plasticity-learning-and-memory-in-the-era-of%C3%A2-epitranscriptomics
#16
REVIEW
Laura J Leighton, Ke Ke, Esmi L Zajaczkowski, Jordan Edmunds, Robert C Spitale, Timothy W Bredy
In this short review, we highlight recent findings in the emerging field of epitranscriptomic mechanisms and discuss their potential role in neural plasticity, learning and memory. These include the influence of RNA modifications on activity-induced RNA structure states, RNA editing and RNA localization, and how qualitative state changes in RNA increase the functional diversity and information-carrying capacity of RNA molecules. We predict that RNA modifications may be just as important for synaptic plasticity and memory as quantitative changes in transcript and protein abundance, but with the added advantage of not being required to signal back to the nucleus, and therefore better suited to be coordinated with the temporal dynamics of learning...
September 19, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#17
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28923016/5-hydroxymethylcytosine-is-highly-dynamic-across-human-fetal-brain-development
#18
Helen Spiers, Eilis Hannon, Leonard C Schalkwyk, Nicholas J Bray, Jonathan Mill
BACKGROUND: Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory...
September 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28922739/o-glcnac-transferase-regulates-transcriptional-activity-of-human-oct4
#19
Sandii Constable, Jae-Min Lim, Krithika Vaidyanathan, Lance Wells
O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc...
October 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28921125/exogenous-cannabinoid-efficacy-merely-a-pharmacokinetic-interaction
#20
Jennifer H Martin, Jennifer Schneider, Catherine J Lucas, Peter Galettis
Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained. Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported. Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation...
September 18, 2017: Clinical Pharmacokinetics
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