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https://www.readbyqxmd.com/read/29343442/the-transcription-factor-stat6-mediates-direct-repression-of-inflammatory-enhancers-and-limits-activation-of-alternatively-polarized-macrophages
#1
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
#2
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
#3
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...
January 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29300726/regulation-of-circadian-clock-transcriptional-output-by-clock-bmal1
#4
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 4, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29289754/estrogen-regulated-transcription-mammary-gland-and-uterus
#5
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 transcription of genes involved in numerous cellular functions. The E2-dependent engagement of ERα across the genome, collectively called the ERα 'cistrome', exhibits a high degree of complexity and plasticity. The ERα cistrome is defined by pioneer factors, transcription co-factors, posttranslational modifications of ERα, the chromatin environment, and cross talk with other signaling pathways...
December 29, 2017: Steroids
https://www.readbyqxmd.com/read/29212143/targeting-cistrome-and-dysregulated-transcriptome-of-post-mpn-saml
#6
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
#7
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...
December 4, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29181434/androgen-receptor-ar-cistrome-in-prostate-differentiation-and-cancer-progression
#8
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
#9
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...
November 3, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29100329/cancer-cell-line-specific-co-factors-modulate-the-foxm1-cistrome
#10
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
https://www.readbyqxmd.com/read/29092952/timer-a-web-server-for-comprehensive-analysis-of-tumor-infiltrating-immune-cells
#11
Taiwen Li, Jingyu Fan, Binbin Wang, Nicole Traugh, Qianming Chen, Jun S Liu, Bo Li, X Shirley Liu
Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29092931/cistrome-cancer-a-web-resource-for-integrative-gene-regulation-modeling-in-cancer
#12
Shenglin Mei, Clifford A Meyer, Rongbin Zheng, Qian Qin, Qiu Wu, Peng Jiang, Bo Li, Xiaohui Shi, Binbin Wang, Jingyu Fan, Celina Shih, Myles Brown, Chongzhi Zang, X Shirley Liu
Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29059155/reactivation-of-androgen-receptor-regulated-lipid-biosynthesis-drives-the-progression-of-castration-resistant-prostate-cancer
#13
W Han, S Gao, D Barrett, M Ahmed, D Han, J A Macoska, H H He, C Cai
Androgen receptor (AR) is a transcriptional activator that, in prostate cells, stimulates gene expression required for various cellular functions, including metabolisms and proliferation. AR signaling is also essential for the development of hormone-dependent prostate cancer (PCa) and its activity can be blocked by androgen-deprivation therapies (ADTs). Although PCa patients initially respond well to ADTs, the cancer inevitably relapses and progresses to lethal castration-resistant prostate cancer (CRPC). Although AR activity is generally restored in CRPC despite the castrate level of androgens, it is unclear whether AR signaling is significantly reprogrammed...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29027168/chip-re-chip-co-occupancy-analysis-by-sequential-chromatin-immunoprecipitation
#14
Timothy V Beischlag, Gratien G Prefontaine, Oliver Hankinson
Chromatin immunoprecipitation (ChIP) exploits the specific interactions between DNA and DNA-associated proteins. It can be used to examine a wide range of experimental parameters. A number of proteins bound at the same genomic location can identify a multi-protein chromatin complex where several proteins work together to regulate gene transcription or chromatin configuration. In many instances, this can be achieved using sequential ChIP; or simply, ChIP-re-ChIP. Whether it is for the examination of specific transcriptional or epigenetic regulators, or for the identification of cistromes, the ability to perform a sequential ChIP adds a higher level of power and definition to these analyses...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28925401/endogenous-androgen-receptor-proteomic-profiling-reveals-genomic-subcomplex-involved-in-prostate-tumorigenesis
#15
S Stelloo, E Nevedomskaya, Y Kim, L Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W M van Weerden, A F M Altelaar, A M Bergman, W Zwart
Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28887309/phosphorylation-of-the-oncogenic-transcription-factor-erg-in-prostate-cells-dissociates-polycomb-repressive-complex-2-allowing-target-gene-activation
#16
Vivekananda Kedage, Brady G Strittmatter, Paige B Dausinas, Peter C Hollenhorst
In ∼50% of prostate cancers, chromosomal rearrangements cause the fusion of the promoter and 5'-UTR of the androgen-regulated TMPRSS2 (transmembrane protease, serine 2) gene to the open reading frame of ERG, encoding an ETS family transcription factor. This fusion results in expression of full-length or N-terminally truncated ERG protein in prostate epithelia. ERG is not expressed in normal prostate epithelia, but when expressed, it promotes tumorigenesis via altered gene expression, stimulating epithelial-mesenchymal transition, cellular migration/invasion, and transformation...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28873439/crispr-focus-a-web-server-for-designing-focused-crispr-screening-experiments
#17
Qingyi Cao, Jian Ma, Chen-Hao Chen, Han Xu, Zhi Chen, Wei Li, X Shirley Liu
The recently developed CRISPR screen technology, based on the CRISPR/Cas9 genome editing system, enables genome-wide interrogation of gene functions in an efficient and cost-effective manner. Although many computational algorithms and web servers have been developed to design single-guide RNAs (sgRNAs) with high specificity and efficiency, algorithms specifically designed for conducting CRISPR screens are still lacking. Here we present CRISPR-FOCUS, a web-based platform to search and prioritize sgRNAs for CRISPR screen experiments...
2017: PloS One
https://www.readbyqxmd.com/read/28870774/ets-transcription-factor-family-member-gabpa-contributes-to-vitamin-d-receptor-target-gene-regulation
#18
Sabine Seuter, Antonio Neme, Carsten Carlberg
Binding motifs of the ETS-domain transcription factor GABPA are found with high significance below the summits of the vitamin D receptor (VDR) cistrome. VDR is the nuclear receptor for the biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In this study, we determined the GABPA cistrome in THP-1 human monocytes and found that it is comprised of 3822 genomic loci, some 20% of which were modulated by 1,25(OH)2D3. The GABPA cistrome showed a high overlap rate with accessible chromatin and the pioneer transcription factor PU...
September 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28863148/a-conceptual-and-computational-framework-for-modelling-and-understanding-the-non-equilibrium-gene-regulatory-networks-of-mouse-embryonic-stem-cells
#19
Richard B Greaves, Sabine Dietmann, Austin Smith, Susan Stepney, Julianne D Halley
The capacity of pluripotent embryonic stem cells to differentiate into any cell type in the body makes them invaluable in the field of regenerative medicine. However, because of the complexity of both the core pluripotency network and the process of cell fate computation it is not yet possible to control the fate of stem cells. We present a theoretical model of stem cell fate computation that is based on Halley and Winkler's Branching Process Theory (BPT) and on Greaves et al.'s agent-based computer simulation derived from that theoretical model...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28820292/p53-binding-sites-in-normal-and-cancer-cells-are-characterized-by-distinct-chromatin-context
#20
Feifei Bao, Peter R LoVerso, Jeffrey N Fisk, Victor B Zhurkin, Feng Cui
The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo...
August 18, 2017: Cell Cycle
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