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Histone variants

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https://www.readbyqxmd.com/read/28623522/h3-k27m-mutations-are-extremely-rare-in-posterior-fossa-group-a-ependymoma
#1
Scott Ryall, Miguel Guzman, Samer K Elbabaa, Betty Luu, Stephen C Mack, Michal Zapotocky, Michael D Taylor, Cynthia Hawkins, Vijay Ramaswamy
BACKGROUND: Mutations in the tail of histone H3 (K27M) are frequently found in pediatric midline high-grade glioma's but have rarely been reported in other malignancies. Recently, recurrent somatic nucleotide variants in histone H3 (H3 K27M) have been reported in group A posterior fossa ependymoma (EPN_PFA), an entity previously described to have no recurrent mutations. However, the true incidence of H3 K27M mutations in EPN_PFA is unknown. METHODS: In order to discern the frequency of K27M mutations in histone H3 in EPN_PFA, we analyzed 151 EPN_PFA previously profiled with genome-wide methylation arrays using a validated droplet digital PCR assay...
June 16, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28617799/p53-and-tap63-participate-in-the-recombination-dependent-pachytene-arrest-in-mouse-spermatocytes
#2
Marina Marcet-Ortega, Sarai Pacheco, Ana Martínez-Marchal, Helena Castillo, Elsa Flores, Maria Jasin, Scott Keeney, Ignasi Roig
To protect germ cells from genomic instability, surveillance mechanisms ensure meiosis occurs properly. In mammals, spermatocytes that display recombination defects experience a so-called recombination-dependent arrest at the pachytene stage, which relies on the MRE11 complex-ATM-CHK2 pathway responding to unrepaired DNA double-strand breaks (DSBs). Here, we asked if p53 family members-targets of ATM and CHK2-participate in this arrest. We bred double-mutant mice combining a mutation of a member of the p53 family (p53, TAp63, or p73) with a Trip13 mutation...
June 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28615324/hihimap-single-cell-quantitation-of-histones-and-histone-post-translational-modifications-across-the-cell-cycle-by-high-throughput-imaging
#3
Linda Zane, Fleur Chapus, Gianluca Pegoraro, Tom Misteli
We describe HiHiMap (High-throughput Histone Mapping), a high-throughput imaging method to measure histone and histone post-translational modifications (PTM) in single cells. HiHiMap uses imaging-based quantification of DNA and Cyclin A to stage individual cells in the cell cycle to determine the levels of histone or histone PTMs in each stage of the cell cycle. As proof-of-principle, we apply HiHiMap to measure the level of 21 core histones, histone variants and PTMs in primary, immortalized and transformed cells...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28614057/dual-effects-of-constitutively-active-androgen-receptor-and-full-length-androgen-receptor-for-n-cadherin-regulation-in-prostate-cancer
#4
Félicie Cottard, Pauline Ould Madi-Berthélémy, Eva Erdmann, Frédérique Schaff-Wendling, Céline Keime, Tao Ye, Jean-Emmanuel Kurtz, Jocelyn Céraline
Constitutively active androgen receptor (AR) variants have been involved in the expression of mesenchymal markers such as N-cadherin in prostate cancer (PCa). However, the underlying molecular mechanisms remain elusive. It remains unclear, whether N-cadherin gene (CDH2) is a direct transcriptional target of AR variants or whether the observed upregulation is due to indirect effects through additional regulatory factors. Moreover, the specific contribution of full-length AR and AR variants in N-cadherin regulation in PCa has never been explored deeply...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609657/ack1-tnk2-regulates-histone-h4-tyr88-phosphorylation-and-ar-gene-expression-in-castration-resistant-prostate-cancer
#5
Kiran Mahajan, Pavani Malla, Harshani R Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J Lawrence, Nupam P Mahajan
The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28608921/whole-exome-sequencing-reveals-critical-genes-underlying-metastasis-in-esophageal-squamous-cell-carcinoma
#6
Wei Dai, Josephine Mun Yee Ko, Sheyne Sta Ana Choi, Zhouyou Yu, Luwen Ning, Hong Zheng, Vinod Gopalan, Kin Tak Chan, Nikki Pui-Yue Lee, Kwok Wah Chan, Simon Ying-Kit Law, Alfred King-Yin Lam, Maria Li Lung
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers due to a high frequency of metastasis. However, little is known about the genomic landscape of metastatic ESCC. To identify the genetic alterations that underlie ESCC metastasis, whole-exome sequencing (WES) was performed for 41 primary tumors and 15 lymph nodes (LNs) with metastatic ESCC. Eleven cases included matched primary tumors, synchronous LN metastases and non-neoplastic mucosa. Approximately 50-76% of the mutations identified in primary tumors appeared in the synchronous LN metastases...
June 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28607146/epigenetic-transcriptional-memory-of-gal-genes-depends-on-growth-in-glucose-and-the-tup1-transcription-factor-in-saccharomyces-cerevisiae
#7
Varun Sood, Ivelisse Cajigas, Agustina D'Urso, William H Light, Jason H Brickner
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2 and GAL7 These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory...
June 12, 2017: Genetics
https://www.readbyqxmd.com/read/28600325/hira-deficiency-in-muscle-fibers-causes-hypertrophy-and-susceptibility-to-oxidative-stress
#8
Nicolas Valenzuela, Benjamin Soibam, Lerong Li, Jing Wang, Lauren A Byers, Yu Liu, Robert J Schwartz, M David Stewart
Nucleosome assembly proceeds through DNA replication-coupled or replication-independent mechanisms. For skeletal myocytes, whose nuclei have permanently exited the cell cycle, replication-independent assembly is the only mode available for chromatin remodeling. For this reason, any nucleosome composition alterations accompanying transcriptional responses to physiological signals must occur through a DNA replication-independent pathway. HIRA is the histone chaperone primarily responsible for replication-independent incorporation of histone variant H3...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28598437/centromeres-are-maintained-by-fastening-cenp-a-to-dna-and-directing-an-arginine-anchor-dependent-nucleosome-transition
#9
Lucie Y Guo, Praveen Kumar Allu, Levani Zandarashvili, Kara L McKinley, Nikolina Sekulic, Jennine M Dawicki-McKenna, Daniele Fachinetti, Glennis A Logsdon, Ryan M Jamiolkowski, Don W Cleveland, Iain M Cheeseman, Ben E Black
Maintaining centromere identity relies upon the persistence of the epigenetic mark provided by the histone H3 variant, centromere protein A (CENP-A), but the molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define the contributions of each of the three candidate CENP-A nucleosome-binding domains (two on CENP-C and one on CENP-N) to CENP-A stability using gene replacement and rapid protein degradation. Surprisingly, the most conserved domain, the CENP-C motif, is dispensable...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28598241/critical-histone-post-translational-modifications-for-centromere-function-and-propagation
#10
Tatsuo Fukagawa
The centromere is a critical genomic region that enables faithful chromosome segregation during mitosis, and must be distinguishable from other genomic regions to facilitate establishment of the kinetochore. The centromere-specific histone H3-variant CENP-A forms a special nucleosome that functions as a marker for centromere specification. In addition to the CENP-A nucleosomes, there are additional H3 nucleosomes that have been identified in centromeres, both of which are predicted to exhibit specific features...
June 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28596481/mislocalization-of-centromeric-histone-h3-variant-cenp-a-contributes-to-chromosomal-instability-cin-in-human-cells
#11
Roshan L Shrestha, Grace S Ahn, Mae I Staples, Kizhakke M Sathyan, Tatiana S Karpova, Daniel R Foltz, Munira A Basrai
Chromosomal instability (CIN) is a hallmark of many cancers and a major contributor to tumorigenesis. Centromere and kinetochore associated proteins such as the evolutionarily conserved centromeric histone H3 variant CENP-A, associate with centromeric DNA for centromere function and chromosomal stability. Stringent regulation of cellular CENP-A levels prevents its mislocalization in yeast and flies to maintain genome stability. CENP-A overexpression and mislocalization are observed in several cancers and reported to be associated with increased invasiveness and poor prognosis...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588720/synergistic-activity-of-the-histone-deacetylase-inhibitor-trichostatin-a-and-the-proteasome-inhibitor-ps-341-against-taxane-resistant-ovarian-cancer-cell-lines
#12
Xin Jin, Yong Fang, Yi Hu, Jing Chen, Wei Liu, Gang Chen, Mei Gong, Peng Wu, Tao Zhu, Shixuan Wang, Jianfeng Zhou, Hui Wang, Ding Ma, Kezhen Li
Although a combination of platinum- and taxane-based chemotherapy is recommended for at least 70% patients with ovarian cancer as treatment subsequent to surgery, the initial response to the chemotherapy is not durable and tumors become resistant. Histone deacetylase and proteasome inhibitors are novel therapeutic agents. However, the moderate antitumoral effect of the inhibitors has restricted their clinical use when used as single agents. The aim of the present study was to investigate the synergistic activity of trichostatin A (TSA) and PS-341 in ovarian cancer cells, along with the investigation of the molecular mechanisms of taxane resistance...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28587112/is-there-a-role-for-genomics-in-the-management-of-hypertension
#13
REVIEW
Jacopo Burrello, Silvia Monticone, Fabrizio Buffolo, Martina Tetti, Franco Veglio, Tracy A Williams, Paolo Mulatero
Hypertension (HTN) affects about 1 billion people worldwide and the lack of a single identifiable cause complicates its treatment. Blood pressure (BP) levels are influenced by environmental factors, but there is a strong genetic component. Linkage analysis has identified several genes involved in Mendelian forms of HTN and the associated pathophysiological mechanisms have been unravelled, leading to targeted therapies. The majority of these syndromes are due to gain-of-function or loss-of-functions mutations, resulting in an alteration of mineralocorticoid, glucocorticoid, or sympathetic pathways...
May 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28585440/ep300-contributes-to-high-altitude-adaptation-in-tibetans-by-regulating-nitric-oxide-production
#14
Wang-Shan Zheng, Yao-Xi He, Chao-Ying Cui, Luobu Ouzhu, Quzong Deji, Yi Peng, Cai-Juan Bai, Zhuoma Duoji, Lanzi Gongga, Ba Bian, Kangzhuo Baima, Yong-Yue Pan, la Qu, Min Kang, Yangji Ciren, Yangji Baima, Wei Guo, la Yang, Hui Zhang, Xiao-Ming Zhang, Yong-Bo Guo, Shu-Hua Xu, Hua Chen, Sheng-Guo Zhao, Yuan Cai, Shi-Ming Liu, Tian-Yi Wu, Xue-Bin Qi, Bing Su
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans...
May 18, 2017: Zoological Research
https://www.readbyqxmd.com/read/28572608/genetic-insights-into-juvenile-idiopathic-arthritis-derived-from-deep-whole-genome-sequencing
#15
Laiping Wong, Kaiyu Jiang, Yanmin Chen, James N Jarvis
Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequencing fidelity. Genome wide SNP density analysis identified 18 SNP hotspots with comparison to the 1000 Genome Projects (1KGP) data. A subset of the genes adjacent to SNP hotspots showed statistically significant enrichment in immunological processes...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28564596/the-histone-variant-macroh2a1-is-a-brca1%C3%A2-ubiquitin-ligase-substrate
#16
Beom-Jun Kim, Doug W Chan, Sung Yun Jung, Yue Chen, Jun Qin, Yi Wang
The breast- and ovarian-cancer-specific tumor suppressor BRCA1 and its heterodimeric partner BARD1 contain RING domains that implicate them as E3 ubiquitin ligases. Despite extensive efforts, the bona fide substrates of BRCA1/BARD1 remain elusive. Here, we used recombinant GST fused to four UBA domains to enrich ubiquitinated proteins followed by a Lys-ε-Gly-Gly (diGly) antibody to enrich ubiquitinated tryptic peptides. This tandem affinity purification method coupled with mass spectrometry identified 101 putative BRCA1/BARD1 E3 substrates...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28552951/common-variants-near-ikzf1-are-associated-with-primary-sj%C3%A3-gren-s-syndrome-in-han-chinese
#17
Susu Qu, Yang Du, Suhua Chang, Liyuan Guo, Kechi Fang, Yongzhe Li, Fengchun Zhang, Kunlin Zhang, Jing Wang
Primary Sjögren's syndrome (pSS) is a systematic autoimmune disease with evidence of genetic predisposition. The IKZF1 (IKAROS family zinc finger 1 (Ikaros)) gene is located at 7p12.2, encodes a transcription factor related to chromatin remodeling, regulates lymphocyte differentiation, and has been reported to be associated with some autoimmune diseases. However, there have been no reports of an association between IKZF1 and pSS. To investigate the possibility of an association between the IKZF1 locus and pSS, we selected two single nucleotide polymorphisms (SNPs) in the IKZF1 locus, rs4917129 and rs4917014, based on a detailed analysis of genome-wide association study (GWAS) data and performed genotyping in 665 Han Chinese pSS patients and 863 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28552470/cd4-t-cells-from-hiv-1-patients-with-impaired-th1-effector-responses-to-mycobacterium-tuberculosis-exhibit-diminished-histone-and-nucleoprotein-signatures
#18
Lillian Seu, James A Mobley, Paul A Goepfert
HIV+ patients have an increased risk for tuberculosis disease despite clinical management with ARTs. We established a culture model of Mtb-infection in PBMCs from HIV+ PPD+ donors on suppressive ART (median 6.4years) with negligible viral loads (median<50copies/mL) and stable CD4+ T cell counts (517cells/mm^3). We observed that HIV+ patient lymphocytes harbored a recruitment defect to Mtb-infected monocytes. To investigate these immune defects on a per cell basis, purified CD4+ T cells from HIV patients were assessed by label-free quantification protein mass spectrometry...
May 25, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28551330/histopathologic-evaluation-of-atypical-neurofibromatous-tumors-and-their-transformation-into-malignant-peripheral-nerve-sheath-tumor-in-neurofibromatosis-1-patients-a-consensus-overview
#19
Markku M Miettinen, Cristina R Antonescu, Christopher D M Fletcher, Aerang Kim, Alexander J Lazar, Martha M Quezado, Karlyne M Reilly, Anat Stemmer-Rachamimov, Douglas R Stewart, David Viskochil, Brigitte Widemann, Arie Perry
Neurofibromatosis 1 (NF1) patients develop multiple neurofibromas, with 8-15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, following a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant trans-formation of neurofibromas. Nuclear atypia alone is generally insignificant...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28549158/chd2-regulates-chromatin-for-proper-gene-expression-toward-differentiation-in-mouse-embryonic-stem-cells
#20
Yuichiro Semba, Akihito Harada, Kazumitsu Maehara, Shinya Oki, Chikara Meno, Jun Ueda, Kazuo Yamagata, Atsushi Suzuki, Mitsuho Onimaru, Jumpei Nogami, Seiji Okada, Koichi Akashi, Yasuyuki Ohkawa
Chromatin reorganization is necessary for pluripotent stem cells, including embryonic stem cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state for appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) is required to maintain the differentiation potential of mouse ESCs. Chd2-depleted ESCs showed suppressed expression of developmentally regulated genes upon differentiation and subsequent differentiation defects without affecting gene expression in the undifferentiated state...
May 26, 2017: Nucleic Acids Research
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