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https://www.readbyqxmd.com/read/28717181/discovery-of-novel-human-gene-regulatory-modules-from-gene-co-expression-and-promoter-motif-analysis
#1
Shisong Ma, Michael Snyder, Savithramma P Dinesh-Kumar
Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif's enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697333/the-dyt6-dystonia-protein-thap1-regulates-myelination-within-the-oligodendrocyte-lineage
#2
Dhananjay Yellajoshyula, Chun-Chi Liang, Samuel S Pappas, Silvia Penati, Angela Yang, Rodan Mecano, Ravindran Kumaran, Stephanie Jou, Mark R Cookson, William T Dauer
The childhood-onset motor disorder DYT6 dystonia is caused by loss-of-function mutations in the transcription factor THAP1, but the neurodevelopmental processes in which THAP1 participates are unknown. We find that THAP1 is essential for the timing of myelination initiation during CNS maturation. Conditional deletion of THAP1 in the CNS retards maturation of the oligodendrocyte (OL) lineage, delaying myelination and causing persistent motor deficits. The CNS myelination defect results from a cell-autonomous requirement for THAP1 in the OL lineage and is recapitulated in developmental assays performed on OL progenitor cells purified from Thap1 null mice...
July 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28682643/yy1-is-required-for-posttranscriptional-stability-of-sox2-and-oct4-proteins
#3
Mary C Wallingford, Jacob Hiller, Kun Zhang, Jesse Mager
Yinyang1 (YY1) participates in protein-DNA, protein-RNA, and protein-protein interactions and regulates developmental processes and disease mechanisms. YY1 interactions regulate a range of important biological functions, including oocyte maturation, epithelial to mesenchymal transition, and vascular endothelial growth factor (VEGF) signaling. We tested the hypothesis that YY1 is required for inner cell mass (ICM) lineage commitment during preimplantation development. In this study, we document gene expression patterns and protein localization of key transcription factors in Yy1 global, tissue-specific, and dsRNA-mediated knockout/down embryos...
July 6, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28661460/the-novel-hdac8-inhibitor-wk2-16-attenuates-lipopolysaccharide-activated-matrix-metalloproteinase-9-expression-in-human-monocytic-cells-and-improves-hypercytokinemia-in-vivo
#4
Jing-Shiun Jan, Yung-Chen Chou, Yu-Wen Cheng, Chih-Kuang Chen, Wei-Jan Huang, George Hsiao
Dysregulated human monocytes/macrophages can synthesize and secrete matrix metalloproteinases (MMPs), which play important roles in the progression of sepsis. In this study, we investigated the effects and mechanism of a novel histone deacetylase (HDAC8) inhibitor, (E)-N-hydroxy-4-methoxy-2-(biphenyl-4-yl)cinnamide (WK2-16), on MMP-9 production and activation in stimulated human monocytic THP-1 cells. Our results demonstrated that the acetylation level of structural maintenance of chromosomes 3 (SMC3) was up-regulated by WK2-16 in THP-1 cells...
June 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28649789/beyond-mitf-multiple-transcription-factors-directly-regulate-the-cellular-phenotype-in-melanocytes-and-melanoma
#5
REVIEW
Hannah E Seberg, Eric Van Otterloo, Robert A Cornell
MITF governs multiple steps in the development of melanocytes, including specification from neural crest, growth, survival, and terminal differentiation. In addition, the level of MITF activity determines the phenotype adopted by melanoma cells, whether invasive, proliferative, or differentiated. However, MITF does not act alone. Here we review literature on the transcription factors that co-regulate MITF-dependent genes. ChIP-seq studies have indicated that the transcription factors SOX10, YY1, and TFAP2A co-occupy subsets of regulatory elements bound by MITF in melanocytes...
June 26, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28593745/ox-ldl-increases-microrna-29a-transcription-through-up-regulating-yy1-and-stat1-in-macrophages
#6
Dongdong Jian, Bing Dai, Xiaotong Hu, Qiang Yao, Li Zhang, Jianhua Zhu
Macrophages and oxidized low-density lipoprotein (ox-LDL) have been verified playing vital roles in the pathogenesis of atherosclerosis (AS). Previous studies demonstrated that microRNA-29a (miR-29a) was up-regulated in many atherogenic process and cells thus acting as an important participant in AS. But the detailed regulation mechanism of miR-29a in AS has not been fully understood. In our study, we demonstrated a positive feedback loop ox-LDL-SRA-miR-29a. Furthermore, we found that YY1 and STAT1 were up-regulated in ox-LDL stimulating macrophages followed by translocating in the nucleus and binding to the transcriptional promoter region of miR-29a thus leading to the increase of miR-29a expression...
June 7, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28592880/expression-and-transcriptional-regulation-of-human-atp6v1a-gene-in-gastric-cancers
#7
Pin Wang, Lei Wang, Jie Sha, Guochun Lou, Nannan Lu, Bo Hang, Jian-Hua Mao, Xiaoping Zou
Recent studies demonstrate that the invasion and metastasis of gastric cancer (GC) is closely associated with a multi-subunit vacuolar H+-ATPase (V-ATPase). Here we investigated the expression and role of the human ATP6V1A gene that encodes the catalytic subunit A of V-ATPase in GC. We found that ATP6V1A expression level is significantly elevated in GCs compared to normals, but GC patients with higher expression levels of ATP6V1A have a better prognosis. Genomic analysis revealed that APT6V1A copy number is gained in a small fraction of GC patients and lost in a minimum number...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592290/dna-methylation-based-chromatin-compartments-and-chip-seq-profiles-reveal-transcriptional-drivers-of-prostate-carcinogenesis
#8
Poppy Simmonds, Erick Loomis, Edward Curry
BACKGROUND: Profiles of DNA methylation of many tissues relevant in human disease have been obtained from microarrays and are publicly available. These can be used to generate maps of chromatin compartmentalization, demarcating open and closed chromatin across the genome. Additionally, large sets of genome-wide transcription factor binding profiles have been made available thanks to ChIP-seq technology. METHODS: We have identified genomic regions with altered chromatin compartmentalization in prostate adenocarcinoma tissue relative to normal prostate tissue, using DNA methylation microarray data from The Cancer Genome Atlas...
June 7, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28589902/transcription-factor-yin-yang-2-is-a-novel-regulator-of-the-p53-p21-axis
#9
Vivi Kasim, Yu-Dan Xie, Hui-Min Wang, Can Huang, Xue-Song Yan, Wei-Qi Nian, Xiao-Dong Zheng, Makoto Miyagishi, Shou-Rong Wu
Yin Yang 2 (YY2) is a multifunctional zinc-finger transcription factor that belongs to YY family. Unlike the well-characterized YY1, our understanding regarding the biological functions of YY2 is still very limited. Here we found for the first time that in contrast to YY1, which had been reported to be oncogenic, the expression level of YY2 in tumor cells and/or tissues was downregulated compared with its expression level in the normal ones. We also demonstrated that YY2 exerts biological function contrary to YY1 in cell proliferation...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587405/mirna-186-inhibits-prostate-cancer-cell-proliferation-and-tumor-growth-by-targeting-yy1-and-cdk6
#10
Shu Lu, Ming-Shan Wang, Pei-Jie Chen, Qiang Ren, Peiming Bai
microRNAs (miRNAs) are known to be important in tumor initiation and progression. Recent studies have demonstrated that miR-186 is critical in several types of cancer, including human non-small cell lung cancer, bladder cancer and pancreatic ductal adenocarcinoma. However, the functions of miR-186 in prostate cancer (PCa) are still unclear. In the present study, downregulation of miR-186 in PCa cells was detected when compared with the normal prostate cell line. When miR-186 overexpressed in PCa cells, cell proliferation in vitro was evidently inhibited as shown using cell counting kit-8 assays and cell-cycle analysis, and tumor growth in vivo was decreased as shown by tumor growth assays in nude mice...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28580685/yy1-expression-is-sufficient-for-the-maintenance-of-cardiac-progenitor-cell-state
#11
Serge Gregoire, Guang Li, Anthony C Sturzu, Robert J Schwartz, Sean M Wu
During cardiac development, DNA binding transcription factors and epigenetic modifiers regulate gene expression in cardiac progenitor cells (CPCs). We have previously shown that YY1 is essential for the commitment of mesodermal precursors into CPCs. However, the role of YY1 in the maintenance of CPC phenotype and their differentiation into cardiomyocytes is unknown. In this study, we found, by genome-wide transcriptional profiling and phenotypic assays, that YY1 overexpression prevents cardiomyogenic differentiation and maintains the proliferative capacity of CPCs...
June 5, 2017: Stem Cells
https://www.readbyqxmd.com/read/28575647/yy1-haploinsufficiency-causes-an-intellectual-disability-syndrome-featuring-transcriptional-and-chromatin-dysfunction
#12
Michele Gabriele, Anneke T Vulto-van Silfhout, Pierre-Luc Germain, Alessandro Vitriolo, Raman Kumar, Evelyn Douglas, Eric Haan, Kenjiro Kosaki, Toshiki Takenouchi, Anita Rauch, Katharina Steindl, Eirik Frengen, Doriana Misceo, Christeen Ramane J Pedurupillay, Petter Stromme, Jill A Rosenfeld, Yunru Shao, William J Craigen, Christian P Schaaf, David Rodriguez-Buritica, Laura Farach, Jennifer Friedman, Perla Thulin, Scott D McLean, Kimberly M Nugent, Jenny Morton, Jillian Nicholl, Joris Andrieux, Asbjørg Stray-Pedersen, Pascal Chambon, Sophie Patrier, Sally A Lynch, Susanne Kjaergaard, Pernille M Tørring, Charlotte Brasch-Andersen, Anne Ronan, Arie van Haeringen, Peter J Anderson, Zöe Powis, Han G Brunner, Rolph Pfundt, Janneke H M Schuurs-Hoeijmakers, Bregje W M van Bon, Stefan Lelieveld, Christian Gilissen, Willy M Nillesen, Lisenka E L M Vissers, Jozef Gecz, David A Koolen, Giuseppe Testa, Bert B A de Vries
Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and as an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations. Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome...
June 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28566949/the-potential-role-of-neuroinflammation-and-transcription-factors-in-parkinson-disease
#13
Prafulla Chandra Tiwari, Rishi Pal
Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors-notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)-which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors...
March 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28536180/yy1-and-ctcf-orchestrate-a-3d-chromatin-looping-switch-during-early-neural-lineage-commitment
#14
Jonathan A Beagan, Michael T Duong, Katelyn R Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline V Lachanski, Daniel R Gillis, Jennifer E Phillips-Cremins
CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here, we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naïve/primed pluripotency to multipotent primary neural progenitor cells (NPCs)...
July 2017: Genome Research
https://www.readbyqxmd.com/read/28512649/purification-and-characterization-of-schwann-cells-from-adult-human-skin-and-nerve
#15
Jo Anne Stratton, Ranjan Kumar, Sarthak Sinha, Prajay Shah, Morgan Stykel, Yuval Shapira, Rajiv Midha, Jeff Biernaskie
Despite its modest capacity for regeneration, peripheral nervous system injury often results in significant long-term disability. Supplementing peripheral nervous system injury with autologous Schwann cells (SCs) may serve to rejuvenate the postinjury environment to enhance regeneration and ultimately improve functional outcomes. However, human nerve-derived SC (hN-SC) collection procedures require invasive surgical resection. Here, we describe the characterization of SCs from adult human skin (hSk-SCs) of four male donors ranging between 27 and 46 years old...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28505004/a-subset-of-malignant-mesotheliomas-in-young-adults-are-associated-with-recurrent-ewsr1-fus-atf1-fusions
#16
Patrice Desmeules, Philippe Joubert, Lei Zhang, Hikmat A Al-Ahmadie, Christopher D Fletcher, Efsevia Vakiani, Deborah F Delair, Natasha Rekhtman, Marc Ladanyi, William D Travis, Cristina R Antonescu
Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28492540/nmi-inhibits-cancer-stem-cell-traits-by-downregulating-htert-in-breast-cancer
#17
Xu Feng, Xiangdong Xu, Xiangsheng Xiao, Kun Zou, Wendan Yu, Jiali Wu, Ranran Tang, Yue Gao, Jiaojiao Hao, Xinrui Zhao, Yina Liao, Yiming Chen, Wenlin Huang, Wei Guo, Lan Kang, Wuguo Deng
N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this study, we investigated the regulation of NMI on CSCs traits in breast cancer and uncovered the underlying molecular mechanisms. We found that NMI was lowly expressed in breast cancer stem cells (BCSCs)-enriched populations...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28489564/yy1-promotes-hdac1-expression-and-decreases-sensitivity-of-hepatocellular-carcinoma-cells-to-hdac-inhibitor
#18
Sheng Dong, Xiang Ma, Zusen Wang, Bing Han, Hao Zou, Zehua Wu, Yunjin Zang, Likun Zhuang
YY1 is a DNA-binding transcription factor and reported to be involved in cancer progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this study, firstly, we identified two drug-response profiles to HDACi in HCC cell lines, while our results showed that HDAC1 expression was positively correlated with YY1 in HCC cell lines and primary tumor tissues...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488543/the-transcription-factor-foxa1-induces-epithelial-ovarian-cancer-tumorigenesis-and-progression
#19
Li-Li Wang, Yin-Ling Xiu, Xi Chen, Kai-Xuan Sun, Shuo Chen, Dan-Dan Wu, Bo-Liang Liu, Yang Zhao
FOXA1 (forkhead box A1), a member of the FOXA transcription factor superfamily, plays an important role in tumor occurrence and development. However, the relationship between FOXA1 and ovarian cancer has not been reported. We examined normal ovarian tissue and ovarian cancer tissue and found increased FOXA1 expression in the cancer tissue. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays demonstrated that transfection with small interfering RNA to silence FOXA1 (si-FOXA1) in ovarian cancer cell lines decreased cell proliferation and induced apoptosis and S-phase arrest...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28485541/yy1-directly-suppresses-myct1-leading-to-laryngeal-tumorigenesis-and-progress
#20
Si-Yao Qu, Yuan-Yuan Sun, Yun-Hui Li, Zhen-Ming Xu, Wei-Neng Fu
YY1 is a key transcription factor and plays different roles in various cancers. However, role and mechanism of YY1 in laryngeal cancer are still unknown. YY1 and MYCT1 mRNA and protein levels were detected by Real-time RT-PCR and Western Blot methods, respectively. Binding of YY1 to MYCT1 promoter was predicted and confirmed by bioinformatics and chromatin immunoprecipitation assays, respectively. MYCT1 promoter activity was assessed by dual luciferase assay system. Laryngeal cancer cell proliferation, migration, and apoptosis were evaluated by cell viability, colony formation, cell scratch assay, transwell assay, and flow cytometry methods, respectively...
June 2017: Cancer Medicine
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