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Chromatin-associated RNA

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https://www.readbyqxmd.com/read/29229769/cytoplasmic-polyadenylation-mediated-translational-control-of-maternal-mrnas-directs-maternal-to-zygotic-transition
#1
Cecilia Lanny Winata, Maciej Łapiński, Leszek Pryszcz, Candida Vaz, Muhammad Hisyam Bin Ismail, Srikanth Nama, Hajira Shreen Hajan, Serene Gek Ping Lee, Vladimir Korzh, Prabha Sampath, Vivek Tanavde, Sinnakaruppan Mathavan
In the earliest stages of animal development following fertilization, maternally deposited mRNAs direct biological processes to the point of zygotic genome activation (ZGA). These maternal mRNAs undergo cytoplasmic polyadenylation (CPA), suggesting translational control of their activation. To elucidate the biological role of CPA during embryogenesis, we performed genome-wide polysome profiling at several stages of zebrafish development. Our analysis revealed a correlation between CPA and polysome association dynamics, demonstrating a coupling of translation to the CPA of maternal mRNAs...
December 11, 2017: Development
https://www.readbyqxmd.com/read/29227193/ddx5-p68-associated-lncrna-loc284454-is-differentially-expressed-in-human-cancers-and-modulates-gene-expression
#2
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...
December 11, 2017: RNA Biology
https://www.readbyqxmd.com/read/29222118/purine-and-pyrimidine-triple-helix-forming-oligonucleotides-recognize-qualitatively-different-target-sites-at-the-ribosomal-dna-locus
#3
Rodrigo Maldonado, Michael Filarsky, Ingrid Grummt, Gernot Längst
Triplexes are non-canonical DNA structures, which are functionally associated with regulation of gene expression through ncRNA targeting to chromatin. Based on the rules of Hoogsteen base pairing, poly-purine sequences of a duplex can potentially form triplex structures with single-stranded oligonucleotides. Prediction of triplex-forming sequences by bioinformatics analyses have revealed enrichment of potential triplex targeting sites (TTS) at regulatory elements, mainly in promoters and enhancers, suggesting a potential function of RNA-DNA triplexes in transcriptional regulation...
December 8, 2017: RNA
https://www.readbyqxmd.com/read/29222117/pre-mrna-processing-includes-n6-methylation-of-adenosine-residues-that-are-retained-in-mrna-exons-and-the-fallacy-of-rna-epigenetics
#4
Robert B Darnell, Shengdong Ke, James E Darnell
By using a cell fraction technique that separates chromatin associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown that residues in exons are methylated (m6A) in nascent pre-mRNA and remain methylated in the same exonic residues in nucleoplasmic and cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of demethylation in mRNA exons that would correspond to so-called "epigenetic" demethylation. The turnover rate of mRNA molecules is faster depending on m6A content in HeLa cell mRNA suggesting specification of mRNA stability may be the major role of m6A exon modification...
December 8, 2017: RNA
https://www.readbyqxmd.com/read/29221147/long-noncoding-rna-linc00673-epigenetically-suppresses-klf4-by-interacting-with-ezh2-and-dnmt1-in-gastric-cancer
#5
Ming-Chen Ba, Hui Long, Shu-Zhong Cui, Yuan-Feng Gong, Zhao-Fei Yan, Yin-Bing Wu, Yi-Nuo Tu
Long non-coding RNAs (lncRNAs), a variety of transcripts without protein coding ability, have recently been reported to play vital roles in gastric cancer (GC) development and progression. However, the biological role of long non-coding RNA LINC00673 in GC is not fully known. In the study, we found that LINC00673 expression was dramatically higher in gastric cancer tissues compared with adjacent normal tissues, and positively associated with lymph node metastasis, distant metastasis and TNM stage in patients...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212533/subtracting-the-sequence-bias-from-partially-digested-mnase-seq-data-reveals-a-general-contribution-of-tfiis-to-nucleosome-positioning
#6
Gabriel Gutiérrez, Gonzalo Millán-Zambrano, Daniel A Medina, Antonio Jordán-Pla, José E Pérez-Ortín, Xenia Peñate, Sebastián Chávez
BACKGROUND: TFIIS stimulates RNA cleavage by RNA polymerase II and promotes the resolution of backtracking events. TFIIS acts in the chromatin context, but its contribution to the chromatin landscape has not yet been investigated. Co-transcriptional chromatin alterations include subtle changes in nucleosome positioning, like those expected to be elicited by TFIIS, which are elusive to detect. The most popular method to map nucleosomes involves intensive chromatin digestion by micrococcal nuclease (MNase)...
December 7, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29212152/prpf8-is-important-for-brca1-mediated-homologous-recombination
#7
David O Onyango, Gabriella Lee, Jeremy M Stark
Disruption of RNA splicing causes genome instability, which could contribute to cancer etiology. Furthermore, RNA splicing is an emerging anti-cancer target. Thus, we have evaluated the influence of the spliceosome factor PRPF8 and the splicing inhibitor Pladienolide B (PlaB) on homologous recombination (HR). We find that PRPF8 depletion and PlaB treatment cause a specific defect in homology-directed repair (HDR), and single strand annealing (SSA), which share end resection as a common intermediate, and BRCA1 as a required factor...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211713/runx3-programs-cd8-t-cell-residency-in-non-lymphoid-tissues-and-tumours
#8
J Justin Milner, Clara Toma, Bingfei Yu, Kai Zhang, Kyla Omilusik, Anthony T Phan, Dapeng Wang, Adam J Getzler, Toan Nguyen, Shane Crotty, Wei Wang, Matthew E Pipkin, Ananda W Goldrath
Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control TRM cell differentiation and homeostasis are not fully understood. Here we show that mouse TRM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of TRM cell differentiation and homeostasis...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29208650/transcriptional-profiling-of-saccharomyces-cerevisiae-reveals-the-impact-of-variation-of-a-single-transcription-factor-on-differential-gene-expression-in-4nqo-fermentable-and-non-fermentable-carbon-sources
#9
Xiaqing Rong-Mullins, Michael C Ayers, Mahmoud Summers, Jennifer E G Gallagher
Cellular metabolism can change the potency of a chemical's tumorigenicity. 4-nitroquinoline-1-oxide (4NQO) is a tumorigenic drug widely used on animal models for cancer research. Polymorphisms of the transcription factor, Yrr1, confer different levels of resistance to 4NQO in Saccharomyces cerevisiae To study how different Yrr1 alleles regulate gene expression leading to resistance, transcriptomes of three isogenic Scerevisiae strains carrying different Yrr1 alleles were profiled via RNA sequencing (RNA-Seq) and chromatin immunoprecipitation coupled with sequencing (ChIP-Seq) in presence and absence of 4NQO...
December 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29207671/ginkgo-biloba-extract-egb-761-induced-upregulation-of-lincrna-p21-inhibits-colorectal-cancer-metastasis-by-associating-with-ezh2
#10
Tingting Liu, Junzhong Zhang, Zhongqiu Chai, Gang Wang, Naiqiang Cui, Bing Zhou
EGb 761, the standard ginkgo biloba extract, is frequently prescribed in traditional Chinese medicine. Currently, there is no research focusing on its role in human colorectal cancer progression. In our study, we determined the anti-metastatic effect of EGb 761 on colorectal cancer cells and further explored the potential underlying regulatory mechanism. The cell migration and invasion assay indicated that EGb 761 treatment of colorectal cancer cells induced inhibition of cell migration and invasion ability in a concentration-dependent manner...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203764/3d-genome-of-multiple-myeloma-reveals-spatial-genome-disorganization-associated-with-copy-number-variations
#11
Pengze Wu, Tingting Li, Ruifeng Li, Lumeng Jia, Ping Zhu, Yifang Liu, Qing Chen, Daiwei Tang, Yuezhou Yu, Cheng Li
The Hi-C method is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple myeloma (MM) and how it associates with genomic variation and gene expression. Our results show that Hi-C interaction matrices are biased by copy number variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS data can improve the detection of translocations...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29201167/chaf1a-the-largest-subunit-of-the-chromatin-assembly-factor-1-complex-regulates-the-growth-of-h1299-human-non-small-cell-lung-cancer-cells-by-inducing-g0-g1-cell-cycle-arrest
#12
Tanzhen Liu, Jingjing Wei, Chao Jiang, Chen Wang, Xiaoqin Zhang, Yan Du, Jianqiang Li, Hui Zhao
Chromatin assembly factor 1 subunit A (CHAF1A) is the largest subunit of the chromatin assembly factor 1 (CAF-1) complex that is implicated in the assembly of nucleosomes on newly synthesized DNA. The aim of the present study was to determine its expression and biological function in non-small cell lung cancer (NSCLC). The current study examined the levels of CHAF1A expression in 22 samples of NSCLC and corresponding normal lung tissues. Subsequently, endogenous CHAF1A expression in H1299 NSCLC cells was knocked down via lentiviral delivery of CHAF1A-targeting short hairpin RNA (shRNA), and cell proliferation, colony formation and cell cycle distribution were measured...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29199022/ctcf-mediated-chromatin-loops-between-promoter-and-gene-body-regulate-alternative-splicing-across-individuals
#13
Mariana Ruiz-Velasco, Manjeet Kumar, Mang Ching Lai, Pooja Bhat, Ana Belen Solis-Pinson, Alejandro Reyes, Stefan Kleinsorg, Kyung-Min Noh, Toby J Gibson, Judith B Zaugg
The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA...
November 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/29196535/wnk1-kinase-and-the-termination-factor-pcf11-connect-nuclear-mrna-export-with-transcription
#14
Adam Volanakis, Kinga Kamieniarz-Gdula, Margarita Schlackow, Nick J Proudfoot
Nuclear gene transcription is coordinated with transcript release from the chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the mammalian mRNA export pathway even though it was previously established as a critical regulator of ion homeostasis in the cytoplasm. Our data reveal that WNK1 phosphorylates the termination factor PCF11 on its RNA polymerase II (Pol II) C-terminal domain (CTD)-interacting domain (CID)...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29186125/promoter-bound-mettl3-maintains-myeloid-leukaemia-by-m6a-dependent-translation-control
#15
Isaia Barbieri, Konstantinos Tzelepis, Luca Pandolfini, Junwei Shi, Gonzalo Millán-Zambrano, Samuel C Robson, Demetrios Aspris, Valentina Migliori, Andrew J Bannister, Namshik Han, Etienne De Braekeleer, Hannes Ponstingl, Alan Hendrick, Christopher R Vakoc, George S Vassiliou, Tony Kouzarides
N6-methyladenosine (m6A) is an abundant internal RNA modification in both coding and non-coding RNAs that is catalysed by the METTL3-METTL14 methyltransferase complex. However, the specific role of these enzymes in cancer is still largely unknown. Here we define a pathway that is specific for METTL3 and is implicated in the maintenance of a leukaemic state. We identify METTL3 as an essential gene for growth of acute myeloid leukaemia cells in two distinct genetic screens. Downregulation of METTL3 results in cell cycle arrest, differentiation of leukaemic cells and failure to establish leukaemia in immunodeficient mice...
November 27, 2017: Nature
https://www.readbyqxmd.com/read/29179037/nuclear-myosin-1-associates-with-papillomavirus-e2-regulatory-protein-and-influences-viral-replication
#16
Eve Sankovski, Aare Abroi, Mart Ustav, Mart Ustav
Nuclear myosin 1c (NM1) associates with RNA polymerases and is a partner in the chromatin remodeling complex B-WICH. This complex, which also contains WSTF and SNF2h proteins, is involved in transcriptional regulation. We report herein that papillomavirus protein E2 binds to NM1 and co-precipitates with the WSTF and SNF2h proteins. Our data suggest that E2 associates with the cellular B-WICH complex through binding to NM1. E2 and NM1 associate via their N-terminal domains and this interaction is ATP dependent...
November 24, 2017: Virology
https://www.readbyqxmd.com/read/29177737/immunoprecipitation-of-rna-dna-hybrids-from-budding-yeast
#17
Aziz El Hage, David Tollervey
During transcription, the nascent transcript behind an elongating RNA polymerase (RNAP) can invade the DNA duplex and hybridize with the complementary DNA template strand, generating a three-stranded "R-loop" structure, composed of an RNA:DNA duplex and an unpaired non-template DNA strand. R-loops can be strongly associated with actively transcribed loci by all RNAPs including the mitochondrial RNA polymerase (mtRNAP). In this chapter, we describe two protocols for the detection of RNA:DNA hybrids in living budding yeast cells, one that uses conventional chromatin immunoprecipitation (ChIP-qPCR) and one that uses DNA:RNA immunoprecipitation (DRIP-qPCR)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29177731/topoisomerase-i-and-genome-stability-the-good-and-the-bad
#18
Jang-Eun Cho, Sue Jinks-Robertson
Topoisomerase I (Top1) resolves torsional stress that accumulates during transcription, replication and chromatin remodeling by introducing a transient single-strand break in DNA. The cleavage activity of Top1 has opposing roles, either promoting or destabilizing genome integrity depending on the context. Resolution of transcription-associated negative supercoils, for example, prevents pairing of the nascent RNA with the DNA template (R-loops) as well as DNA secondary structure formation. Reduced Top1 levels thus enhance CAG repeat contraction, somatic hypermutation, and class switch recombination...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29171881/rna-n6-methyladenosine-methyltransferase-mettl3-promotes-liver-cancer-progression-through-ythdf2-dependent-post-transcriptional-silencing-of-socs2
#19
Mengnuo Chen, Lai Wei, Cheuk-Ting Law, Felice Ho-Ching Tsang, Jialing Shen, Carol Lai-Hung Cheng, Long-Hin Tsang, Daniel Wai-Hung Ho, David Kung-Chun Chiu, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
Epigenetic alterations immensely contributed to human carcinogenesis. Conventional epigenetic studies predominantly focused on DNA methylation, histone modifications, and chromatin remodeling. Recently, diverse and reversible chemical modifications on RNAs emerge as a new layer of epigenetic regulation. N6-methyladenosine (m6A) is the most abundant chemical modification on eukaryotic mRNA and is important to the regulation of mRNA stability, splicing, and translation. Using transcriptome sequencing, we discovered that METTL3 (methyltransferase like 3), a major RNA N6-adenosine methyltransferase, was significantly up-regulated in human hepatocellular carcinoma (HCC) and multiple solid tumors...
November 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29158440/cohesin-facilitates-zygotic-genome-activation-in-zebrafish
#20
Michael Meier, Jenny Grant, Amy Dowdle, Amarni Thomas, Jennifer Gerton, Philippe Collas, Justin M O'Sullivan, Julia A Horsfield
At zygotic genome activation (ZGA), changes in chromatin structure are associated with new transcription immediately following the maternal-to-zygotic transition (MZT). The nuclear architectural proteins, cohesin and CCCTC-binding factor (CTCF), contribute to chromatin structure and gene regulation. We show here that normal cohesin function is important for ZGA in zebrafish. Depletion of cohesin subunit Rad21 delays ZGA without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA whereas complete abrogation is lethal...
November 20, 2017: Development
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