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Chromatin-associated RNA

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https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#1
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28633434/psip1-p75-promotes-tumorigenicity-in-breast-cancer-cells-by-promoting-the-transcription-of-cell-cycle-genes
#2
Deepak K Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo-Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G Prasanth, Ashish Lal, Kannanganattu V Prasanth
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma...
June 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28628087/chromatin-enriched-lncrnas-can-act-as-cell-type-specific-activators-of-proximal-gene-transcription
#3
Michael S Werner, Matthew A Sullivan, Rohan N Shah, Rangarajan D Nadadur, Adrian T Grzybowski, Vasiliy Galat, Ivan P Moskowitz, Alexander J Ruthenburg
We recently described a new class of long noncoding RNAs (lncRNAs) that are distinguished by especially tight chromatin association and whose presence is strongly correlated to expression of nearby genes. Here, we examine the cis-enhancer mechanism of this class of chromatin-enriched RNA (cheRNA) across multiple human cell lines. cheRNAs are largely cell type specific and provide the most reliable chromatin signature to predict cis-gene transcription in every human cell type examined. Targeted depletion of three cheRNAs decreases expression of their neighboring genes, indicating potential co-activator function, and single-molecule fluorescence in situ hybridization (smFISH) of one cheRNA-distal target gene pair suggests a spatial overlap consistent with a role in chromosome looping...
June 19, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28620275/genome-wide-target-analyses-of-otx2-homeoprotein-in-postnatal-cortex
#4
Akiko Sakai, Ryuichiro Nakato, Yiwei Ling, Xubin Hou, Norikazu Hara, Tomoya Iijima, Yuchio Yanagawa, Ryozo Kuwano, Shujiro Okuda, Katsuhiko Shirahige, Sayaka Sugiyama
Juvenile brain has a unique time window, or critical period, in which neuronal circuits are remodeled by experience. Mounting evidence indicates the importance of neuronal circuit rewiring in various neurodevelopmental disorders of human cognition. We previously showed that Otx2 homeoprotein, essential for brain formation, is recaptured during postnatal maturation of parvalbumin-positive interneurons (PV cells) to activate the critical period in mouse visual cortex. Cortical Otx2 is the only interneuron-enriched transcription factor known to regulate the critical period, but its downstream targets remain unknown...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28615992/overexpression-of-lncrna-hoxa11-as-promotes-cell-epithelial-mesenchymal-transition-by-repressing-mir-200b-in-non-small-cell-lung-cancer
#5
Jian-Hui Chen, Li-Yang Zhou, Suo Xu, Yu-Long Zheng, Yu-Feng Wan, Cheng-Ping Hu
BACKGROUND: Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). METHODS: The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28615201/the-latency-associated-nuclear-antigen-of-kaposi-s-sarcoma-associated-herpesvirus-inhibits-expression-of-sumo-sentrin-specific-peptidase-6-to-facilitate-latency-establishment
#6
Xiaoxi Lin, Rui Sun, Fang Zhang, Yuan Gao, Lianghua Bin, Ke Lan
Kaposi's sarcoma-associated herpesvirus (KSHV), belonging to γ-herpesviridae, typically displays two different phases in its lifecycle, the latent phase and the lytic phase. Latent-associated nuclear antigen (LANA), the primary viral product during latency, has been reported to bind to a series of cellular gene promoters to modulate gene transcription. To systemically elucidate the cellular genes regulated by LANA, we identified genome-wide LANA binding sites by chromatin immunoprecipitation coupled with sequencing (ChIP-seq)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28614747/rna-mediated-regulation-of-heterochromatin
#7
REVIEW
Whitney L Johnson, Aaron F Straight
The formation of condensed, transcriptionally repressed heterochromatin is essential for controlling gene expression throughout development, silencing parasitic DNA elements, and for genome stability and inheritance. Cells employ diverse mechanisms for controlling heterochromatin states through proteins that modify DNA and histones. An emerging theme is that chromatin-associated RNAs play important roles in regulating heterochromatin proteins by controlling their initial recruitment to chromatin, their stable association with chromatin, their spread along chromatin, or their enzymatic activity...
June 11, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28611249/a-herpesviral-immediate-early-protein-promotes-transcription-elongation-of-viral-transcripts
#8
Hannah L Fox, Jill A Dembowski, Neal A DeLuca
Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28610652/novel-insights-into-the-role-of-cell-free-seminal-mrnas-on-semen-quality-and-cryotolerance-of-spermatozoa-in-bulls-bos-taurus
#9
Munivenkatappa Shilpa, Sellappan Selvaraju, Venkataswamy GirishKumar, Sivashanmugam Parthipan, Krishnan B Binsila, Arunachalam Arangasamy, Janivara Parameshwaraiah Ravindra
The aim of the present study was to ascertain the effectiveness of seminal plasma mRNAs as markers to assess the reproductive performance of bulls. Semen samples (33 ejaculates) from 11 bulls were evaluated for sperm kinematic and functional parameters. Total RNA was isolated from cell-free seminal (cfs) using TRIzol LS reagent and the concentration of cfs-RNA was 24.4±2.3µgmL-1 seminal plasma. The cfs-RNA was fragmented to a size of 25-500bp. Of the cfs-mRNAs screened using real time PCR, expression of protamine 1 (PRM1) was positively (P<0...
June 14, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28609483/histone-posttranslational-modifications-predict-specific-alternative-exon-subtypes-in-mammalian-brain
#10
Qiwen Hu, Eun Ji Kim, Jian Feng, Gregory R Grant, Elizabeth A Heller
A compelling body of literature, based on next generation chromatin immunoprecipitation and RNA sequencing of reward brain regions indicates that the regulation of the epigenetic landscape likely underlies chronic drug abuse and addition. It is now critical to develop highly innovative computational strategies to reveal the relevant regulatory transcriptional mechanisms that may underlie neuropsychiatric disease. We have analyzed chromatin regulation of alternative splicing, which is implicated in cocaine exposure in mice...
June 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28605403/power-and-sample-size-calculations-for-high-throughput-sequencing-based-experiments
#11
Chung-I Li, David C Samuels, Ying-Yong Zhao, Yu Shyr, Yan Guo
Power/sample size (power) analysis estimates the likelihood of successfully finding the statistical significance in a data set. There has been a growing recognition of the importance of power analysis in the proper design of experiments. Power analysis is complex, yet necessary for the success of large studies. It is important to design a study that produces statistically accurate and reliable results. Power computation methods have been well established for both microarray-based gene expression studies and genotyping microarray-based genome-wide association studies...
June 9, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28596772/epigenetic-regulation-of-matrix-metalloproteinase-1-and-3-expression-in-mycobacterium-tuberculosis-infection
#12
Rachel C Moores, Sara Brilha, Frans Schutgens, Paul T Elkington, Jon S Friedland
In pulmonary tuberculosis (TB), the inflammatory immune response against Mycobacterium tuberculosis (Mtb) is associated with tissue destruction and cavitation, which drives disease transmission, chronic lung disease, and mortality. Matrix metalloproteinase (MMP)-1 is a host enzyme critical for the development of cavitation. MMP expression has been shown to be epigenetically regulated in other inflammatory diseases, but the importance of such mechanisms in Mtb-associated induction of MMP-1 is unknown. We investigated the role of changes in histone acetylation in Mtb-induced MMP expression using inhibitors of histone deacetylases (HDACs) and histone acetyltransferases (HAT), HDAC siRNA, promoter-reporter constructs, and chromatin immunoprecipitation assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28593035/smchd1-regulates-a-limited-set-of-gene-clusters-on-autosomal-chromosomes
#13
Amanda G Mason, Roderick C Slieker, Judit Balog, Richard J L F Lemmers, Chao-Jen Wong, Zizhen Yao, Jong-Won Lim, Galina N Filippova, Enrico Ne, Rabi Tawil, Bas T Heijmans, Stephen J Tapscott, Silvère M van der Maarel
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is in most cases caused by a contraction of the D4Z4 macrosatellite repeat on chromosome 4 (FSHD1) or by mutations in the SMCHD1 or DNMT3B gene (FSHD2). Both situations result in the incomplete epigenetic repression of the D4Z4-encoded retrogene DUX4 in somatic cells, leading to the aberrant expression of DUX4 in the skeletal muscle. In mice, Smchd1 regulates chromatin repression at different loci, having a role in CpG methylation establishment and/or maintenance...
2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28592530/kaposi-s-sarcoma-associated-herpesvirus-utilizes-and-manipulates-rna-n-6-adenosine-methylation-to-promote-lytic-replication
#14
Fengchun Ye, E Ricky Chen, Timothy W Nilsen
N(6)-adenosine methylation (m(6)A) is the most common post-transcriptional RNA modification in mammalian cells. We found that most transcripts encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) undergo m(6)A modification. The levels of m(6)A-modified mRNAs increase substantially upon stimulation for lytic replication. Blocking m(6)A inhibits splicing of the pre-mRNA encoding replication transcription activator (RTA), a key KSHV lytic switch protein, and halts viral lytic replication. We identified several m(6)A sites in RTA pre-mRNA crucial for splicing through interactions with YTH domain containing 1 (YTHDC1), an m(6)A nuclear reader protein, in conjunction with serine/arginine-rich splicing factor 3 (SRSF3) and SRSF10...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28587678/smchd1-regulates-a-limited-set-of-gene-clusters-on-autosomal-chromosomes
#15
Amanda G Mason, Roderick C Slieker, Judit Balog, Richard J L F Lemmers, Chao-Jen Wong, Zizhen Yao, Jong-Won Lim, Galina N Filippova, Enrico Ne, Rabi Tawil, Bas T Heijmans, Stephen J Tapscott, Silvère M van der Maarel
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is in most cases caused by a contraction of the D4Z4 macrosatellite repeat on chromosome 4 (FSHD1) or by mutations in the SMCHD1 or DNMT3B gene (FSHD2). Both situations result in the incomplete epigenetic repression of the D4Z4-encoded retrogene DUX4 in somatic cells, leading to the aberrant expression of DUX4 in the skeletal muscle. In mice, Smchd1 regulates chromatin repression at different loci, having a role in CpG methylation establishment and/or maintenance...
June 6, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28585565/architecture-of-the-rna-polymerase-ii-paf1c-tfiis-transcription-elongation-complex
#16
Youwei Xu, Carrie Bernecky, Chung-Tien Lee, Kerstin C Maier, Björn Schwalb, Dimitry Tegunov, Jürgen M Plitzko, Henning Urlaub, Patrick Cramer
The conserved polymerase-associated factor 1 complex (Paf1C) plays multiple roles in chromatin transcription and genomic regulation. Paf1C comprises the five subunits Paf1, Leo1, Ctr9, Cdc73 and Rtf1, and binds to the RNA polymerase II (Pol II) transcription elongation complex (EC). Here we report the reconstitution of Paf1C from Saccharomyces cerevisiae, and a structural analysis of Paf1C bound to a Pol II EC containing the elongation factor TFIIS. Cryo-electron microscopy and crosslinking data reveal that Paf1C is highly mobile and extends over the outer Pol II surface from the Rpb2 to the Rpb3 subunit...
June 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28581511/rna-fate-determination-through-cotranscriptional-adenosine-methylation-and-microprocessor-binding
#17
Philip Knuckles, Sarah H Carl, Michael Musheev, Christof Niehrs, Alice Wenger, Marc Bühler
Eukaryotic gene expression is heavily regulated at the transcriptional and post-transcriptional levels. An additional layer of regulation occurs co-transcriptionally through processing and decay of nascent transcripts physically associated with chromatin. This process involves RNA interference (RNAi) machinery and is well documented in yeast, but little is known about its conservation in mammals. Here we show that Dgcr8 and Drosha physically associate with chromatin in murine embryonic stem cells (mES), specifically with a subset of transcribed coding and noncoding genes...
June 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28578223/serpinb2-is-regulated-by-dynamic-interactions-with-pause-release-proteins-and-enhancer-rnas
#18
Lihua Shii, Li Song, Kelly Maurer, Zhe Zhang, Kathleen E Sullivan
The SERPINB2 gene is strongly upregulated in inflammatory states. In monocytes, it can constitute up to 1% of total cellular protein. It functions in protection from proteotoxic stress and plays a role in angioedema. The purpose of this study was to define the roles of enhancer RNAs embedded in the SERPIN gene complex. We found that the upstream enhancer RNAs upregulated SERPINB2 and the enhancer RNAs were expressed prior to those of SERPINB2 mRNA. Studies of the SERPINB2 promoter demonstrated the presence of an RNA polymerase II pause-inducing protein, NELF...
June 1, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28577753/cocaine-induced-chromatin-modifications-associate-with-increased-expression-and-three-dimensional-looping-of-auts2
#19
Olivia Engmann, Benoit Labonté, Amanda Mitchell, Pavel Bashtrykov, Erin S Calipari, Chaggai Rosenbluh, Yong-Hwee E Loh, Deena M Walker, Dominika Burek, Peter J Hamilton, Orna Issler, Rachael L Neve, Gustavo Turecki, Yasmin Hurd, Andrew Chess, Li Shen, Isabelle Mansuy, Albert Jeltsch, Schahram Akbarian, Eric J Nestler
BACKGROUND: Exposure to drugs of abuse alters the epigenetic landscape of the brain's reward regions, such as the nucleus accumbens. We investigated how combinations of chromatin modifications affect genes that regulate responses to cocaine. We focused on Auts2, a gene linked to human evolution and cognitive disorders, which displays strong clustering of cocaine-induced chromatin modifications in this brain region. METHODS: We combined chromosome conformation capture, circularized chromosome conformation capture, and related approaches with behavioral paradigms relevant to cocaine phenotypes...
May 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28575439/mediator-binds-to-boundaries-of-chromosomal-interaction-domains-and-to-proteins-involved-in-dna-looping-rna-metabolism-chromatin-remodeling-and-actin-assembly
#20
Razvan V Chereji, Vasudha Bharatula, Nils Elfving, Jeanette Blomberg, Miriam Larsson, Alexandre V Morozov, James R Broach, Stefan Björklund
Mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to RNA polymerase II in eukaryotes. We have combined biochemical purification of the Saccharomyces cerevisiae Mediator from chromatin with chromatin immunoprecipitation in order to reveal Mediator occupancy on DNA genome-wide, and to identify proteins interacting specifically with Mediator on the chromatin template. Tandem mass spectrometry of proteins in immunoprecipitates of mediator complexes revealed specific interactions between Mediator and the RSC, Arp2/Arp3, CPF, CF 1A and Lsm complexes in chromatin...
May 30, 2017: Nucleic Acids Research
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