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Chromatin-associated LncRNA

Paulo P Amaral, Tommaso Leonardi, Namshik Han, Emmanuelle Viré, Dennis K Gascoigne, Raúl Arias-Carrasco, Magdalena Büscher, Luca Pandolfini, Anda Zhang, Stefano Pluchino, Vinicius Maracaja-Coutinho, Helder I Nakaya, Martin Hemberg, Ramin Shiekhattar, Anton J Enright, Tony Kouzarides
BACKGROUND: The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. RESULTS: We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes...
March 15, 2018: Genome Biology
Sellappan Selvaraju, Sivashanmugam Parthipan, Lakshminarayana Somashekar, B Krishnan Binsila, Atul P Kolte, Arunachalam Arangasamy, Janivara Parameshwaraiah Ravindra, Stephen A Krawetz
With artificial insemination (AI) and other precision dependent assisted reproductive technologies (ART) being followed in large scale in human and animal reproduction, assessing semen quality and fertilizability is under continuous scrutiny. Various tests have been developed to predict semen quality, but so far no single, highly reliable test is available. In this regard, transcriptomic profiling of spermatozoa assumes significance as it carries the information about spermatogenesis, sperm function, and paternal roles in post-fertilization events...
March 14, 2018: Systems Biology in Reproductive Medicine
Yan Liang, Xuedan Chen, Yuanyuan Wu, Juan Li, Shixin Zhang, Kai Wang, Xingying Guan, Kang Yang, Yun Bai
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. Recently, lncRNA CASC9 was shown to be dysregulated in many cancer types, but the mechanisms whereby this occurs remain largely unknown. In this study, we found that CASC9 was significantly upregulated in ESCC tissues, with further analysis revealing that elevated CASC9 expression was associated with ESCC prognosis and metastasis. Furthermore, we found that CASC9 knockdown significantly repressed ESCC migration and invasion in vitro and metastasis in nude mice in vivo...
March 6, 2018: Cell Death and Differentiation
Dorine Jeanne Mariëtte du Mee, Maxim Ivanov, Joseph Paul Parker, Stephen Buratowski, Sebastian Marquardt
Most DNA in the genomes of higher organisms does not code for proteins. RNA Polymerase II (Pol II) transcribes non-coding DNA into long non-coding RNAs (lncRNAs), but biological roles of lncRNA are unclear. We find that mutations in the yeast lncRNA CUT60 result in poor growth. Defective termination of CUT60 transcription causes read-through transcription across the ATP16 gene promoter. Read-through transcription localizes chromatin signatures associated with Pol II elongation to the ATP16 promoter. The act of Pol II elongation across this promoter represses functional ATP16 expression by a Transcriptional Interference (TI) mechanism...
March 5, 2018: ELife
H S Jeffrey Man, Aravin N Sukumar, Gabrielle C Lam, Paul J Turgeon, Matthew S Yan, Kyung Ha Ku, Michelle K Dubinsky, J J David Ho, Jenny Jing Wang, Sunit Das, Nora Mitchell, Peter Oettgen, Michael V Sefton, Philip A Marsden
Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell type-specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for s pliced- t ranscript e ndothelial- e nriched lncRNA (STEEL) in angiogenic potential, macrovascular/microvascular identity, and shear stress responsiveness...
February 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
Valentina Miano, Giulio Ferrero, Valentina Rosti, Eleonora Manitta, Jamal Elhasnaoui, Giulia Basile, Michele De Bortoli
Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoERα-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoERα, including one mapped in proximity of the DSCAM-AS1 lncRNA gene...
February 16, 2018: International Journal of Molecular Sciences
Mariangela Morlando, Alessandro Fatica
Long noncoding RNAs (lncRNAs) are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression...
February 14, 2018: International Journal of Molecular Sciences
En-Hui Li, Xin Zhao, Ce Zhang, Wei Liu
Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells...
February 20, 2018: Yi Chuan, Hereditas
Xue Liu, Dayong Li, Donglei Zhang, Dedong Yin, Yi Zhao, Chengjun Ji, Xianfeng Zhao, Xiaobing Li, Qun He, Runsheng Chen, Songnian Hu, Lihuang Zhu
Natural antisense long noncoding RNAs (lncRNAs) are widespread in many organisms. However, their biological functions remain largely unknown, particularly in plants. We report the identification and characterization of an endogenous lncRNA, TWISTED LEAF (TL), which is transcribed from the opposite strand of the R2R3 MYB transcription factor gene locus, OsMYB60, in rice (Oryza sativa). TL and OsMYB60 were found to be coexpressed in many different tissues, and the expression level of TL was higher than that of OsMYB60...
February 7, 2018: New Phytologist
Weicai Zheng, Aixiang Yu
Although the upregulation of enhancer of zeste homolog 2 (EZH2) expression and downregulation of long non-coding RNA (lncRNA) LET expression are known to be associated with cell apoptosis and proliferation, little is known about the interaction of EZH2 with lncRNA LET. The present study aimed to investigate the interaction of EZH2 and lncRNA LET, and the mechanism of human dermal fibroblast (HDF) proliferation and apoptosis. Tissue samples from 33 burn patients with second- and third-degree burns and 8 controls were collected...
January 25, 2018: International Journal of Molecular Medicine
Yi Zhang, Mohith Manjunath, Shilu Zhang, Deborah Chasman, Sushmita Roy, Jun S Song
Previous genome-wide association studies (GWAS) have identified several common genetic variants that may significantly modulate cancer susceptibility. However, the precise molecular mechanisms behind these associations remain largely unknown; it is often not clear whether discovered variants are themselves functional or merely genetically linked to other functional variants. Here we provide an integrated method for identifying functional regulatory variants associated with cancer and their target genes by combining analyses of expression quantitative trait loci (eQTL), a modified version of allele-specific expression (ASE) that systematically utilizes haplotype information, transcription factor (TF) binding preference, and epigenetic information...
January 19, 2018: Cancer Research
Yifei Miao, Nassim E Ajami, Tse-Shun Huang, Feng-Mao Lin, Chih-Hong Lou, Yun-Ting Wang, Shuai Li, Jian Kang, Hannah Munkacsi, Mano R Maurya, Shakti Gupta, Shu Chien, Shankar Subramaniam, Zhen Chen
The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE)...
January 18, 2018: Nature Communications
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A Boon, Stefanie Dimmeler
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice...
January 16, 2018: Nature Communications
Tengfei Li, Yang Xiao, Tunsheng Huang
Increasing evidence indicates that long non‑coding RNAs (lncRNAs) play an important role in multiple biological processes including cell growth, differentiation, proliferation and invasion. Urothelial carcinoma associated 1 (UCA1) is a highly conserved nuclear ncRNA and a key regulator of cell proliferation and apoptosis in several types of cancers. However, its role in osteosarcoma progression is not well known. In the present study, we aimed to determine the biological role of UCA1 in osteosarcoma progression...
January 3, 2018: Oncology Reports
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
Yanhui Jia, Zhenzhen Li, Weixia Cai, Dan Xiao, Shichao Han, Fu Han, Xiaozhi Bai, Kejia Wang, Yang Liu, Xiaoqiang Li, Hao Guan, Dahai Hu
Molecular mechanisms for macrophage immune responses modulated by SIRT1 during sepsis remain unclear. Here, we show that SIRT1 expression is down-regulated in macrophages from mouse sepsis model or LPS stimulation. SIRT1 expression in macrophages correlates with low levels of a long noncoding RNA (lncRNA)-NONMMUT003701 [named as lncRNA-CCL2]. SIRT1 inhibits lncRNA-CCL2 expression via sustaining a repressive chromatin state in the lncRNA-CCL2 locus. The inflammation cytokines expression is downregulated by knockdown of lncRNA-CCL2...
December 19, 2017: Biochimica et Biophysica Acta
Yu Liu, Ye Yang, Tianlong Wang, Li Wang, Xin Wang, Tiemin Li, Yue Shi, Yawei Wang
OBJECTIVE: Long non-coding RNAs are emerging as key molecules in cancer progression. LncRNA-CCAL has shown to be highly expressed and important in regulating CRC and osteosarcoma development. Nevertheless, the expression and mechanism of CCAL in HCC is still not well understood. METHODS: qRT-PCR and ISH were used to evaluate CCAL expression in HCC tissues and cell lines. Histone H3 methylation and acetylation levels across CCAL promoter region were examined by chromatin immunoprecipitation assays...
December 21, 2017: International Journal of Biological Macromolecules
Qinyu Sun, Qinyu Hao, Kannanganattu V Prasanth
A significant portion of the human genome encodes genes that transcribe long nonprotein-coding RNAs (lncRNAs). A large number of lncRNAs localize in the nucleus, either enriched on the chromatin or localized to specific subnuclear compartments. Nuclear lncRNAs participate in several biological processes, including chromatin organization, and transcriptional and post-transcriptional gene expression, and also act as structural scaffolds of nuclear domains. Here, we highlight recent studies demonstrating the role of lncRNAs in regulating gene expression and nuclear organization in mammalian cells...
December 14, 2017: Trends in Genetics: TIG
Monalisa Das, Arun Renganathan, Shrinivas Nivrutti Dighe, Utsa Bhaduri, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Manchanahalli R Satyanarayana Rao
Long non-coding RNAs (lncRNAs) are emerging as important players in regulation of gene expression in higher eukaryotes. DDX5/p68 RNA helicase protein which is involved in splicing of precursor mRNAs also interacts with lncRNAs like, SRA and mrhl, to modulate gene expression. We performed RIP-seq analysis in HEK293T cells to identify the complete repertoire of DDX5/p68 interacting transcripts including 73 single exonic (SE) lncRNAs. The LOC284454 lncRNA is the second top hit of the list of SE lncRNAs which we have characterized in detail for its molecular features and cellular functions...
February 1, 2018: RNA Biology
Zhonghua Ma, Hesuyuan Huang, Jirong Wang, Yan Zhou, Fuxing Pu, Qinghong Zhao, Peng Peng, Bingqing Hui, Hao Ji, Keming Wang
Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC...
October 13, 2017: Oncotarget
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