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https://www.readbyqxmd.com/read/28436428/neuronal-ifn-beta-induced-pi3k-akt-foxa1-signalling-is-essential-for-generation-of-foxa1-treg-cells
#1
Yawei Liu, Andrea Marin, Patrick Ejlerskov, Louise Munk Rasmussen, Marco Prinz, Shohreh Issazadeh-Navikas
Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice lacking interferon (IFN)-β were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs...
April 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429718/a-computational-systems-approach-identifies-synergistic-specification-genes-that-facilitate-lineage-conversion-to-prostate-tissue
#2
Flaminia Talos, Antonina Mitrofanova, Sarah K Bergren, Andrea Califano, Michael M Shen
To date, reprogramming strategies for generating cell types of interest have been facilitated by detailed understanding of relevant developmental regulatory factors. However, identification of such regulatory drivers often represents a major challenge, as specific gene combinations may be required for reprogramming. Here we show that a computational systems approach can identify cell type specification genes (master regulators) that act synergistically, and demonstrate its application for reprogramming of fibroblasts to prostate tissue...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28419831/molecular-phenotyping-of-transient-postnatal-tyrosine-hydroxylase-neurons-in-the-rat-bed-nucleus-of-the-stria-terminalis
#3
David A Carter
The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype...
April 15, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28419278/integrative-analysis-identifies-targetable-creb1-foxa1-transcriptional-co-regulation-as-a-predictor-of-prostate-cancer-recurrence
#4
Benjamin Sunkel, Dayong Wu, Zhong Chen, Chiou-Miin Wang, Xiangtao Liu, Zhenqing Ye, Aaron M Horning, Joseph Liu, Devalingam Mahalingam, Horacio Lopez-Nicora, Chun-Lin Lin, Paul J Goodfellow, Steven K Clinton, Victor X Jin, Chun-Liang Chen, Tim H-M Huang, Qianben Wang
No abstract text is available yet for this article.
April 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28396520/cytosine-modifications-modulate-the-chromatin-architecture-of-transcriptional-enhancers
#5
Elise A Mahé, Thierry Madigou, Aurélien A Sérandour, Maud Bizot, Stéphane Avner, Frédéric Chalmel, Gaëlle Palierne, Raphaël Métivier, Gilles Salbert
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten Eleven Translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive...
April 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28387346/plk1-regulates-the-repressor-function-of-foxm1b-by-inhibiting-its-interaction-with-the-retinoblastoma-protein
#6
Nishit K Mukhopadhyay, Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Janai R Carr, Yi-Ju Chen, Xiubei Liao, Pradip Raychaudhuri
FoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28367242/the-nor1-oscp1-proteins-in-cancer-from-epigenetic-silencing-to-functional-characterization-of-a-novel-tumor-suppressor
#7
REVIEW
Mei Yi, Jianbo Yang, Wenjuan Li, Xiaoling Li, Wei Xiong, James B McCarthy, Guiyuan Li, Bo Xiang
NOR1 (Oxidored-nitro domain-containing protein 1), also known as OSCP1, was first identified in nasopharyngeal carcinoma (NPC) cells in 2003. NOR1 is evolutionarily conserved among species with its expression is restricted to brain, testis and respiratory epithelial cells. NOR1 was downregulated in NPC and the downregulation associates with poor prognosis. Previous study demonstrated that hypermethylation of NOR1 promoter was observed in NPC and hematological malignancies, which has been believed to be the main epigenetic cause for NOR1 silencing in these cancers...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28361702/a-sequence-based-method-to-predict-the-impact-of-regulatory-variants-using-random-forest
#8
Qiao Liu, Mingxin Gan, Rui Jiang
BACKGROUND: Most disease-associated variants identified by genome-wide association studies (GWAS) exist in noncoding regions. In spite of the common agreement that such variants may disrupt biological functions of their hosting regulatory elements, it remains a great challenge to characterize the risk of a genetic variant within the implicated genome sequence. Therefore, it is essential to develop an effective computational model that is not only capable of predicting the potential risk of a genetic variant but also valid in interpreting how the function of the genome is affected with the occurrence of the variant...
March 14, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28350011/characterisation-of-male-breast-cancer-a-descriptive-biomarker-study-from-a-large-patient-series
#9
Matthew P Humphries, Sreekumar Sundara Rajan, Hedieh Honarpisheh, Gabor Cserni, Jo Dent, Laura Fulford, Lee B Jordan, J Louise Jones, Rani Kanthan, Maria Litwiniuk, Anna Di Benedetto, Marcella Mottolese, Elena Provenzano, Sami Shousha, Mark Stephens, Janina Kulka, Ian O Ellis, Akinwale N Titloye, Andrew M Hanby, Abeer M Shaaban, Valerie Speirs
Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#10
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#11
J Kim, H Jin, J C Zhao, Y A Yang, Y Li, X Yang, X Dong, J Yu
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28282036/heterarchy-of-transcription-factors-driving-basal-and-luminal-cell-phenotypes-in-human-urothelium
#12
Carl Fishwick, Janet Higgins, Lawrence Percival-Alwyn, Arianna Hustler, Joanna Pearson, Sarah Bastkowski, Simon Moxon, David Swarbreck, Chris D Greenman, Jennifer Southgate
Cell differentiation is affected by complex networks of transcription factors that co-ordinate re-organisation of the chromatin landscape. The hierarchies of these relationships can be difficult to dissect. During in vitro differentiation of normal human uro-epithelial cells, formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and RNA-seq was used to identify alterations in chromatin accessibility and gene expression changes following activation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) as a differentiation-initiating event...
March 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28273452/enhancer-mediated-oncogenic-function-of-the-menin-tumor-suppressor-in-breast-cancer
#13
Koen M A Dreijerink, Anna C Groner, Erica S M Vos, Alba Font-Tello, Lei Gu, David Chi, Jaime Reyes, Jennifer Cook, Elgene Lim, Charles Y Lin, Wouter de Laat, Prakash K Rao, Henry W Long, Myles Brown
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER(+) cells...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28270510/down-regulation-of-forkhead-box-protein-a1-foxa1-leads-to-cancer-stem-cell-like-properties-in-tamoxifen-resistant-breast-cancer-cells-through-induction-of-interleukin-6
#14
Noritaka Yamaguchi, Yuji Nakayama, Naoto Yamaguchi
The selective estrogen receptor (ER) modulator tamoxifen inhibits ER signaling in breast cancer cells, and it is used for the treatment of ER-positive breast cancer. However, this type of cancer often acquires resistance to tamoxifen, and a better understanding of the molecular mechanisms underlying tamoxifen-resistance is required. In this study, we established tamoxifen-resistant (TAM-R) breast cancer cells by long-term tamoxifen treatment of ER-positive breast cancer MCF7 cells. In TAM-R cells, expression of not only ERα, a major form of ER in breast cancer, but also its transcriptional partner forkhead box protein A1 (FOXA1) was found to be reduced...
March 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28264478/crosstalk-of-the-androgen-receptor-with-transcriptional-collaborators-potential-therapeutic-targets-for-castration-resistant-prostate-cancer
#15
REVIEW
Daisuke Obinata, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor (AR). Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer (CRPC)...
February 28, 2017: Cancers
https://www.readbyqxmd.com/read/28261581/pbx1-as-pioneer-factor-a-case-still-open
#16
REVIEW
Britta M Grebbin, Dorothea Schulte
Pioneer factors are proteins that can recognize their target sites in barely accessible chromatin and initiate a cascade of events that allows for later transcriptional activation of the respective genes. Pioneer factors are therefore particularly well-suited to initiate cell fate changes. To date, only a small number of pioneer factors have been identified and studied in depth, such as FOXD3/FOXA1, OCT4, or SOX2. Interestingly, several recent studies reported that the PBC transcription factor PBX1 can access transcriptionally inactive genomic loci...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28255498/identification-of-nurr1-exon-4-and-foxa1-exon-3-haplotypes-associated-with-mrna-expression-levels-in-peripheral-blood-lymphocytes-of-parkinson-s-patients-in-small-indian-population
#17
Jayakrishna Tippabathani, Jayshree Nellore, Vaishnavie Radhakrishnan, Somashree Banik, Sonia Kapoor
Here, we study the expression of NURR1 and FOXA1 mRNA in peripheral blood lymphocytes and its haplotypes in coding region in a small Chennai population of India. Thirty cases of Parkinson's patients (PD) with anti-PD medications (20 males aged 65.85 ± 1.19 and 10 females aged 65.7 ± 1.202) and 30 age matched healthy people (20 males aged 68.45 ± 1.282 and 10 females aged 65.8 ± 1.133) were included. The expression of NURR1 and FOXA1 in PBL was detected by Q-PCR and haplotypes were identified by PCR-SSCP...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28238418/foxa1-is-expressed-in-ovarian-mucinous-neoplasms
#18
Georgia Karpathiou, Melany Venet, Mousa Mobarki, Fabien Forest, Celine Chauleur, Michel Peoc'h
FOXA1 is a transcription factor essential for the binding and action of other transcription factors on the chromatin. It is the major regulator of endoderm differentiation. It has important roles in breast, prostate and endometrial cancer. It has never been studied in ovarian tumours. The aim of this study was to investigate its expression in ovarian epithelial neoplasms. A total of 195 primary ovarian epithelial borderline or malignant tumours were immunohistochemically studied for the expression of FOXA1...
April 2017: Pathology
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#19
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28209524/foxa1-in-hpv-associated-carcinomas-its-expression-in-carcinomas-of-the-head-and-neck-and-of-the-uterine-cervix
#20
Georgia Karpathiou, Vanessa Da Cruz, Francois Casteillo, Mousa Mobarki, Jean Marc Dumollard, Celine Chauleur, Fabien Forest, Jean Michel Prades, Michel Peoc'h
BACKGROUND: FOXA1 is a major transcription factor involved in the action of human papilloma virus (HPV). However, it has been never studied in HPV-associated tumors. AIM OF THE STUDY: To investigate its expression in cervical and head and neck tumors. MATERIAL AND METHODS: 63 cervical carcinomas/dysplasias and 152 head and neck squamous cell carcinomas (HNSCC) were immunohistochemically studied for the expression of FOXA1. RESULTS: 63...
February 14, 2017: Experimental and Molecular Pathology
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