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https://www.readbyqxmd.com/read/28306507/structural-and-molecular-mechanisms-of-cytokine-mediated-endocrine-resistance-in-human-breast-cancer-cells
#1
Joshua D Stender, Jerome C Nwachukwu, Irida Kastrati, Yohan Kim, Tobias Strid, Maayan Yakir, Sathish Srinivasan, Jason Nowak, Tina Izard, Erumbi S Rangarajan, Kathryn E Carlson, John A Katzenellenbogen, Xin-Qiu Yao, Barry J Grant, Hon S Leong, Chin-Yo Lin, Jonna Frasor, Kendall W Nettles, Christopher K Glass
Human breast cancers that exhibit high proportions of immune cells and elevated levels of pro-inflammatory cytokines predict poor prognosis. Here, we demonstrate that treatment of human MCF-7 breast cancer cells with pro-inflammatory cytokines results in ERα-dependent activation of gene expression and proliferation, in the absence of ligand or presence of 4OH-tamoxifen (TOT). Cytokine activation of ERα and endocrine resistance is dependent on phosphorylation of ERα at S305 in the hinge domain. Phosphorylation of S305 by IKKβ establishes an ERα cistrome that substantially overlaps with the estradiol (E2)-dependent ERα cistrome...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28302717/regulatory-signatures-of-liver-regeneration-distilled-by-integrative-analysis-of-mrna-histone-methylation-and-proteomics
#2
Yoshihiro Sato, Yasutake Katoh, Mitsuyo Matsumoto, Masaki Sato, Masayuki Ebina, Ari Itoh-Nakadai, Ryo Funayama, Keiko Nakayama, Michiaki Unno, Kazuhiko Igarashi
The capacity of the liver to regenerate is likely to be encoded as a plasticity of molecular networks within the liver. By applying a combination of comprehensive analyses of the epigenome, transcriptome and proteome, we herein depict the molecular landscape of liver regeneration. We demonstrated that histone H3K4 was tri-methylated at the promoter regions of many loci, among which only a fraction including cell-cycle-related genes were transcriptionally up-regulated. A cistrome analysis guided by the histone methylation patterns and the transcriptome identified FOXM1 as the key transcription factor promoting liver regeneration, which was confirmed in vitro using a hepatocarcinoma cell line...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28123935/deletion-of-histone-deacetylase-3-in-adult-beta-cells-improves-glucose-tolerance-via-increased-insulin-secretion
#3
Jarrett R Remsberg, Benjamin N Ediger, Wesley Y Ho, Manashree Damle, Zhenghui Li, Christopher Teng, Cristina Lanzillotta, Doris A Stoffers, Mitchell A Lazar
OBJECTIVE: Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic β-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in β-cells of adult mice. METHODS: An HDAC3 β-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28119415/interaction-with-zmynd11-mediates-opposing-roles-of-ras-responsive-transcription-factors-ets1-and-ets2
#4
Joshua P Plotnik, Peter C Hollenhorst
Aberrant activation of RAS/MAPK signaling is a driver of over one third of all human carcinomas. The homologous transcription factors ETS1 and ETS2 mediate activation of gene expression programs downstream of RAS/MAPK signaling. ETS1 is important for oncogenesis in many tumor types. However, ETS2 can act as an oncogene in some cellular backgrounds, and as a tumor suppressor in others, and the molecular mechanism responsible for this cell-type specific function remains unknown. Here, we show that ETS1 and ETS2 can regulate a cell migration gene expression program in opposite directions, and provide the first comparison of the ETS1 and ETS2 cistromes...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28076760/enriching-the-circadian-proteome
#5
Joseph S Takahashi
Circadian clocks regulate most aspects of physiology and metabolism. Genome-wide approaches have uncovered widespread circadian rhythms in the transcriptome, cistrome, and epigenome of mice, and now two proteomics studies in this issue (Robles et al., 2016; Wang et al., 2016) reveal extensive circadian regulation of the nuclear and phosphoproteome.
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28055971/src-promotes-castration-recurrent-prostate-cancer-through-androgen-receptor-dependent-canonical-and-non-canonical-transcriptional-signatures
#6
Indranil Chattopadhyay, Jianmin Wang, Maochun Qin, Lingqiu Gao, Renae Holtz, Robert L Vessella, Robert W Leach, Irwin H Gelman
Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. Here, we show that activated Src (Src527F) induces androgen-independent growth in human LNCaP cells, concomitant with its ability to induce proliferation/survival genes normally induced by dihydrotestosterone (DHT) in androgen-dependent LNCaP and VCaP cells...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031249/transcription-factor-assisted-loading-and-enhancer-dynamics-dictate-the-hepatic-fasting-response
#7
Ido Goldstein, Songjoon Baek, Diego M Presman, Ville Paakinaho, Erin E Swinstead, Gordon L Hager
Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understand how this complex network regulates the metabolic response to fasting, we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancer features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA), and CCAAT/enhancer binding protein beta (CEBPB)...
March 2017: Genome Research
https://www.readbyqxmd.com/read/28027912/integrative-genomic-approaches-to-dissect-clinically-significant-relationships-between-the-vdr-cistrome-and-gene-expression-in-primary-colon-cancer
#8
REVIEW
Mark D Long, Moray J Campbell
Recently, we undertook a pan-cancer analyses of the nuclear hormone receptor (NR) superfamily in The Cancer Genome Atlas (TCGA), and revealed that the vitamin D receptor (NR1I1/VDR) was commonly and significantly down-regulated specifically in colon adenocarcinoma cohort (COAD). To examine the consequence of down-regulated VDR expression we re-analyzed VDR chromatin immunoprecipitation sequencing (ChIP-Seq) data from LS180 colon cancer cells (GSE31939). This analysis identified 1809 loci that displayed significant (p...
December 24, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27968908/epb41-a-novel-hepatoma-susceptibility-gene-dysregulated-by-c-myc-an-integrative-functional-genomics-study
#9
Xinyu Yang, Dianke Yu, Yanli Ren, Jinyu Wei, Wenting Pan, Changchun Zhou, Liqing Zhou, Yu Liu, Ming Yang
BACKGROUND: Genome-wide association studies (GWAS) have provided insight into cancer genetics. However, molecular mechanisms whereby many susceptibility single nucleotide polymorphisms (SNPs) identified by GWAS promote cancer heritability and risk are unknown. New research strategies to evaluate functionality are needed to systematically study causal genetic variants. METHODS: In this study, we developed an integrative functional genomics method to identify cancer susceptibility SNPs in transcription factor binding sites across the whole genome...
October 2016: Lancet
https://www.readbyqxmd.com/read/27964748/non-coding-single-nucleotide-variants-affecting-estrogen-receptor-binding-and-activity
#10
Amir Bahreini, Kevin Levine, Lucas Santana-Santos, Panayiotis V Benos, Peilu Wang, Courtney Andersen, Steffi Oesterreich, Adrian V Lee
BACKGROUND: Estrogen receptor (ER) activity is critical for the development and progression of the majority of breast cancers. It is known that ER is differentially bound to DNA leading to transcriptomic and phenotypic changes in different breast cancer models. We investigated whether single nucleotide variants (SNVs) in ER binding sites (regSNVs) contribute to ER action through changes in the ER cistrome, thereby affecting disease progression. Here we developed a computational pipeline to identify SNVs in ER binding sites using chromatin immunoprecipitation sequencing (ChIP-seq) data from ER+ breast cancer models...
December 13, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27900343/divergence-and-rewiring-of-regulatory-networks-for-neural-development-between-human-and-other-species
#11
COMMENT
Ping Wang, Dejian Zhao, Shira Rockowitz, Deyou Zheng
Neural and brain development in human and other mammalian species are largely similar, but distinct features exist at the levels of macrostructure and underlying genetic control. Comparative studies of epigenetic regulation and transcription factor (TF) binding in humans, chimpanzees, rodents, and other species have found large differences in gene regulatory networks. A recent analysis of the cistromes of REST/NRSF, a critical transcriptional regulator for the nervous system, demonstrated that REST binding to syntenic genomic regions (i...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27848897/bioinformatics-and-drug-discovery
#12
Xuhua Xia
Bioinformatic analysis can not only accelerate drug target identification and drug candidate screening and refinement, but also facilitate characterization of side effects and predict drug resistance. High-throughput data such as genomic, epigenetic, genome architecture, cistromic, transcriptomic, proteomic, and ribosome profiling data have all made significant contribution to mechanism-based drug discovery and drug repurposing. Accumulation of protein and RNA structures, as well as development of homology modeling and protein structure simulation, coupled with large structure databases of small molecules and metabolites, paved the way for more realistic protein-ligand docking experiments and more informative virtual screening...
November 16, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27802171/cooperative-binding-of-ap-1-and-tead4-modulates-the-balance-between-vascular-smooth-muscle-and-hemogenic-cell-fate
#13
Nadine Obier, Pierre Cauchy, Salam A Assi, Jane Gilmour, Michael Lie-A-Ling, Monika Lichtinger, Maarten Hoogenkamp, Laura Noailles, Peter N Cockerill, Georges Lacaud, Valerie Kouskoff, Constanze Bonifer
The transmission of extracellular signals into the nucleus involves inducible transcription factors, but how different signalling pathways act in a cell type-specific fashion is poorly understood. Here, we studied the regulatory role of the AP-1 transcription factor family in blood development using embryonic stem cell differentiation coupled with genome-wide transcription factor binding and gene expression analyses. AP-1 factors respond to MAP kinase signalling and comprise dimers of FOS, ATF and JUN proteins...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27789702/cistrome-data-browser-a-data-portal-for-chip-seq-and-chromatin-accessibility-data-in-human-and-mouse
#14
Shenglin Mei, Qian Qin, Qiu Wu, Hanfei Sun, Rongbin Zheng, Chongzhi Zang, Muyuan Zhu, Jiaxin Wu, Xiaohui Shi, Len Taing, Tao Liu, Myles Brown, Clifford A Meyer, X Shirley Liu
Chromatin immunoprecipitation, DNase I hypersensitivity and transposase-accessibility assays combined with high-throughput sequencing enable the genome-wide study of chromatin dynamics, transcription factor binding and gene regulation. Although rapidly accumulating publicly available ChIP-seq, DNase-seq and ATAC-seq data are a valuable resource for the systematic investigation of gene regulation processes, a lack of standardized curation, quality control and analysis procedures have hindered extensive reuse of these data...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27672034/crosstalk-between-androgen-and-pro-inflammatory-signaling-remodels-androgen-receptor-and-nf-%C3%AE%C2%BAb-cistrome-to-reprogram-the-prostate-cancer-cell-transcriptome
#15
Marjo Malinen, Einari A Niskanen, Minna U Kaikkonen, Jorma J Palvimo
Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells...
January 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27634452/cell-lineage-specificity-and-role-of-ap-1-in-the-prostate-fibroblast-androgen-receptor-cistrome
#16
Damien A Leach, Vasilios Panagopoulos, Claire Nash, Charlotte Bevan, Axel A Thomson, Luke A Selth, Grant Buchanan
Androgen receptor (AR) signalling in fibroblasts is important in prostate development and carcinogenesis, and is inversely related to prostate cancer mortality. However, the molecular mechanisms of AR action in fibroblasts and other non-epithelial cell types are largely unknown. The genome-wide DNA binding profile of AR in human prostate fibroblasts was identified by chromatin immunoprecipitation sequencing (ChIP-Seq), and found to be common to other fibroblast lines but disparate from AR cistromes of prostate cancer cells and tissue...
September 12, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27617304/epigenetic-remodeling-regulates-transcriptional-changes-between-ovarian-cancer-and-benign-precursors
#17
Kevin M Elias, Megan M Emori, Thomas Westerling, Henry Long, Anna Budina-Kolomets, Fugen Li, Emily MacDuffie, Michelle R Davis, Alexander Holman, Brian Lawney, Matthew L Freedman, John Quackenbush, Myles Brown, Ronny Drapkin
Regulation of lineage-restricted transcription factors has been shown to influence malignant transformation in several types of cancer. Whether similar mechanisms are involved in ovarian cancer pathogenesis is unknown. PAX8 is a nuclear transcription factor that controls the embryologic development of the Müllerian system, including the fallopian tubes. Recent studies have shown that fallopian tube secretory epithelial cells (FTSECs) give rise to the most common form of ovarian cancer, high-grade serous ovarian carcinomas (HGSOCs)...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27610578/cistrome-and-epicistrome-features-shape-the-regulatory-dna-landscape
#18
Ronan C O'Malley, Shao-Shan Carol Huang, Liang Song, Mathew G Lewsey, Anna Bartlett, Joseph R Nery, Mary Galli, Andrea Gallavotti, Joseph R Ecker
No abstract text is available yet for this article.
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27569350/vitamin-d-dependent-chromatin-association-of-ctcf-in-human-monocytes
#19
Antonio Neme, Sabine Seuter, Carsten Carlberg
CCCTC-binding factor (CTCF) is a transcription factor being involved in 3D chromatin organization and displays a highly conserved genome-wide binding pattern. In this study, we report the cistrome of CTCF in THP-1 human monocytes and confirm that from the 40,078 CTCF binding sites nearly 85% are identical with those found in K562 monocytes. Quadruplicate chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that at 2130 loci the association strenght of CTCF with genomic DNA was significantly (p<0...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27549193/comprehensive-analyses-of-tumor-immunity-implications-for-cancer-immunotherapy
#20
Bo Li, Eric Severson, Jean-Christophe Pignon, Haoquan Zhao, Taiwen Li, Jesse Novak, Peng Jiang, Hui Shen, Jon C Aster, Scott Rodig, Sabina Signoretti, Jun S Liu, X Shirley Liu
BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches...
August 22, 2016: Genome Biology
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