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https://www.readbyqxmd.com/read/29716953/correction-comparative-cistromics-reveals-genomic-cross-talk-between-foxa1-and-er%C3%AE-in-tamoxifen-associated-endometrial-carcinomas
#1
(no author information available yet)
No abstract text is available yet for this article.
May 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29705365/progesterone-receptor-regulation-of-uterine-adaptation-for-pregnancy
#2
REVIEW
San-Pin Wu, Rong Li, Francesco J DeMayo
Progesterone acts through the progesterone receptor to direct physiological adaption of the uterus in preparation and completion of pregnancy. Genome-wide transcriptome and cistrome analyses have uncovered new members and novel modifiers of the progesterone signaling pathway. Genetically engineered mice allow functional assessment of newly identified genes in vivo and provide insights on the impact of progesterone receptor-dependent molecular mechanisms on pregnancy at the organ system level. Progesterone receptor isoforms collectively mediate progesterone signaling via their distinct and common downstream target genes, which makes the stoichiometry of isoforms relevant in modifying the progesterone activity...
April 25, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29535630/multifactorial-modes-of-action-of-arsenic-trioxide-in-cancer-cells-as-analyzed-by-classical-and-network-pharmacology
#3
Mona Dawood, Sami Hamdoun, Thomas Efferth
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug's activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2 O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29506156/the-il-4-stat6-ppar%C3%AE-signaling-axis-is-driving-the-expansion-of-the-rxr-heterodimer-cistrome-providing-complex-ligand-responsiveness-in-macrophages
#4
Bence Daniel, Gergely Nagy, Attila Horvath, Zsolt Czimmerer, Ixchelt Cuaranta-Monroy, Szilard Poliska, Tristan T Hays, Sascha Sauer, Jean Francois-Deleuze, Laszlo Nagy
Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive...
February 28, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29473182/the-androgen-receptor-malignancy-shift-in-prostate-cancer
#5
REVIEW
Ben T Copeland, Sumanta K Pal, Eric C Bolton, Jeremy O Jones
BACKGROUND: Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. METHODS: In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications...
May 2018: Prostate
https://www.readbyqxmd.com/read/29471413/combined-cistrome-and-transcriptome-analysis-of-ski-in-aml-cells-identifies-ski-as-a-co-repressor-for-runx1
#6
Christine Feld, Peeyush Sahu, Miriam Frech, Florian Finkernagel, Andrea Nist, Thorsten Stiewe, Uta-Maria Bauer, Andreas Neubauer
SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which >40% harbor SKI binding sites in their proximity, primarily in enhancer regions...
February 20, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29467493/c-jun-ap-1-overexpression-reprograms-er%C3%AE-signaling-related-to-tamoxifen-response-in-er%C3%AE-positive-breast-cancer
#7
Huan He, Indranil Sinha, Rongrong Fan, Lars-Arne Haldosen, Feifei Yan, Chunyan Zhao, Karin Dahlman-Wright
A critical mechanism that has been proposed for transcription regulation by estrogen receptor α (ER) is the tethering of ER to DNA via other transcription factors, such as AP-1. However, genome-wide assessment of the overlap in chromatin binding repertoires of these two transcription factors has not been reported. Here, we show that the AP-1 transcription factor c-Jun interacts with ER and that c-Jun chromatin binding shows extensive overlap with ER binding at the global level. Further, we show that c-Jun overexpression reprograms ER chromatin binding and modulates ER-mediated gene regulation...
February 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29417861/the-potential-of-ar-v7-as-a-therapeutic-target
#8
Takuma Uo, Stephen R Plymate, Cynthia C Sprenger
The androgen receptor variant AR-V7 is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-androgen receptor (AR) therapies in castration-resistant prostate cancer (CRPC). Accordingly, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. Areas covered: We review proposed mechanisms of drug resistance in relation to AR-V7 status, the mechanisms of generation of AR-V7, and its transcriptome, cistrome, and interactome...
March 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29396493/characterizing-steroid-hormone-receptor-chromatin-binding-landscapes-in-male-and-female-breast-cancer
#9
Tesa M Severson, Yongsoo Kim, Stacey E P Joosten, Karianne Schuurman, Petra van der Groep, Cathy B Moelans, Natalie D Ter Hoeve, Quirine F Manson, John W Martens, Carolien H M van Deurzen, Ellis Barbe, Ingrid Hedenfalk, Peter Bult, Vincent T H B M Smit, Sabine C Linn, Paul J van Diest, Lodewyk Wessels, Wilbert Zwart
Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but relapse after hormonal treatment is also noted. The pan-hormonal action of steroid hormonal receptors, including estrogen receptor alpha (ERα), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) in this understudied tumor type remains wholly unexamined. This study reveals genomic cross-talk of steroid hormone receptor action and interplay in human tumors, here in the context of MBC, in relation to the female disease and patient outcome...
February 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29377931/transcriptional-regulatory-control-of-mammalian-nephron-progenitors-revealed-by-multi-factor-cistromic-analysis-and-genetic-studies
#10
Lori L O'Brien, Qiuyu Guo, Emad Bahrami-Samani, Joo-Seop Park, Sean M Hasso, Young-Jin Lee, Alan Fang, Albert D Kim, Jinjin Guo, Trudy M Hong, Kevin A Peterson, Scott Lozanoff, Ramya Raviram, Bing Ren, Ben Fogelgren, Andrew D Smith, Anton Valouev, Andrew P McMahon
Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29343442/the-transcription-factor-stat6-mediates-direct-repression-of-inflammatory-enhancers-and-limits-activation-of-alternatively-polarized-macrophages
#11
Zsolt Czimmerer, Bence Daniel, Attila Horvath, Dominik Rückerl, Gergely Nagy, Mate Kiss, Matthew Peloquin, Marietta M Budai, Ixchelt Cuaranta-Monroy, Zoltan Simandi, Laszlo Steiner, Bela Nagy, Szilard Poliska, Csaba Banko, Zsolt Bacso, Ira G Schulman, Sascha Sauer, Jean-Francois Deleuze, Judith E Allen, Szilvia Benko, Laszlo Nagy
The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29312534/the-pax8-cistrome-in-epithelial-ovarian-cancer
#12
Emily K Adler, Rosario I Corona, Janet M Lee, Norma Rodriguez-Malave, Paulette Mhawech-Fauceglia, Heidi Sowter, Dennis J Hazelett, Kate Lawrenson, Simon A Gayther
PAX8 is a lineage-restricted transcription factor that is expressed in epithelial ovarian cancer (EOC) precursor tissues, and in the major EOC histotypes. Frequent overexpression of PAX8 in primary EOCs suggests this factor functions as an oncogene during tumorigenesis, however, the biological role of PAX8 in EOC development is poorly understood. We found that stable knockdown of PAX8 in EOC models significantly reduced cell proliferation and anchorage dependent growth in vitro, and attenuated tumorigenicity in vivo ...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29309643/androgen-receptor-splice-variants-bind-to-constitutively-open-chromatin-and-promote-abiraterone-resistant-growth-of-prostate-cancer
#13
Yundong He, Ji Lu, Zhenqing Ye, Siyuan Hao, Liewei Wang, Manish Kohli, Donald J Tindall, Benyi Li, Runzhi Zhu, Liguo Wang, Haojie Huang
Androgen receptor (AR) splice variants (ARVs) are implicated in development of castration-resistant prostate cancer (CRPC). Upregulation of ARVs often correlates with persistent AR activity after androgen deprivation therapy (ADT). However, the genomic and epigenomic characteristics of ARV-dependent cistrome and the disease relevance of ARV-mediated transcriptome remain elusive. Through integrated chromatin immunoprecipitation coupled sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, we identified ARV-preferential-binding sites (ARV-PBS) and a set of genes preferentially transactivated by ARVs in CRPC cells...
February 28, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29300726/regulation-of-circadian-clock-transcriptional-output-by-clock-bmal1
#14
Alexandra J Trott, Jerome S Menet
The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29289754/estrogen-regulated-transcription-mammary-gland-and-uterus
#15
Yasmin M Vasquez
Estrogen (E2) plays a central role in the developmental, metabolic and reproductive functions of both males and females. E2 acts via the estrogen receptor alpha (ERα) to regulate the transcription of genes involved in numerous cellular functions. The E2-dependent engagement of ERα across regulatory regions of the genome, termed "enhancers", exhibits a high degree of complexity and plasticity. The E2-transcriptional response is defined by pioneer factors, transcription co-factors, posttranslational modifications of ERα, the chromatin environment, and cross talk with other signaling pathways...
May 2018: Steroids
https://www.readbyqxmd.com/read/29212143/targeting-cistrome-and-dysregulated-transcriptome-of-post-mpn-saml
#16
EDITORIAL
Srdan Verstovsek, Warren Fiskus, Taghi Manshouri, Kapil N Bhalla
No abstract text is available yet for this article.
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29202480/differential-impact-of-rb-status-on-e2f1-reprogramming-in-human-cancer
#17
Christopher McNair, Kexin Xu, Amy C Mandigo, Matteo Benelli, Benjamin Leiby, Daniel Rodrigues, Johan Lindberg, Henrik Gronberg, Mateus Crespo, Bram De Laere, Luc Dirix, Tapio Visakorpi, Fugen Li, Felix Y Feng, Johann de Bono, Francesca Demichelis, Mark A Rubin, Myles Brown, Karen E Knudsen
The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple tumor types, loss of RB function is associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown. Here, analysis of tumor samples and cell-free DNA from patients with advanced prostate cancer showed that direct RB loss was the preferred pathway of disruption in human disease...
January 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29181434/androgen-receptor-ar-cistrome-in-prostate-differentiation-and-cancer-progression
#18
Fengtian Wang, Hari K Koul
Despite the progress in development of better AR-targeted therapies for prostate cancer (PCa), there is no curative therapy for castration-resistant prostate cancer (CRPC). Therapeutic resistance in PCa can be characterized in two broad categories of AR therapy resistance: the first and most prevalent one involves restoration of AR activity despite AR targeted therapy, and the second one involves tumor progression despite blockade of AR activity. As such AR remains the most attractive drug target for CRPC. Despite its oncogenic role, AR signaling also contributes to the maturation and differentiation of prostate luminal cells during development...
2017: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29153843/aberrant-activation-of-a-gastrointestinal-transcriptional-circuit-in-prostate-cancer-mediates-castration-resistance
#19
Shipra Shukla, Joanna Cyrta, Devan A Murphy, Edward G Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W P Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P Koche, Anuradha Gopalan, Deyou Zheng, Mark A Rubin, Howard I Scher, Ping Chi, Yu Chen
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29100329/cancer-cell-line-specific-co-factors-modulate-the-foxm1-cistrome
#20
Yue Wang, Matthew H Ung, Tian Xia, Wenqing Cheng, Chao Cheng
ChIP-seq has been commonly applied to identify genomic occupation of transcription factors (TFs) in a context-specific manner. It is generally assumed that a TF should have similar binding patterns in cells from the same or closely related tissues. Surprisingly, this assumption has not been carefully examined. To this end, we systematically compared the genomic binding of the cell cycle regulator FOXM1 in eight cell lines from seven different human tissues at binding signal, peaks and target genes levels. We found that FOXM1 binding in ER-positive breast cancer cell line MCF-7 are distinct comparing to those in not only other non-breast cell lines, but also MDA-MB-231, ER-negative breast cancer cell line...
September 29, 2017: Oncotarget
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