Abstract:
:To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo H3K4me1 peaks in infected cells were associated with genes implicated in host defenses and apoptosis. Our analysis revealed that 40% of de novo regions contained human/primate-specific Alu transposable elements, enriched in the AluJ and S subtypes. These contained several transcription factor binding sites, including those for members of the MEF2 and ATF families, and LXR and RAR nuclear receptors, all of which have been implicated in macrophage differentiation, survival, and responses to stress and infection. Combining bioinformatics, molecular genetics, and biochemical approaches, we linked genes adjacent to H3K4me1-associated Alu repeats to macrophage metabolic responses against Mtb infection. In particular, we show that LXRα signaling, which reduced Mtb viability 18-fold by altering cholesterol metabolism and enhancing macrophage apoptosis, can be initiated at response elements present in Alu repeats. These studies decipher the mechanism of early macrophage transcriptional responses to Mtb, highlighting the role of Alu element transposition in shaping human transcription programs during innate immunity.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Bouttier M,Laperriere D,Memari B,Mangiapane J,Fiore A,Mitchell E,Verway M,Behr MA,Sladek R,Barreiro LB,Mader S,White JHdoi
10.1093/nar/gkw782subject
Has Abstractpub_date
2016-12-15 00:00:00pages
10571-10587issue
22eissn
0305-1048issn
1362-4962pii
gkw782journal_volume
44pub_type
杂志文章abstract::Specific targeting of protein–nucleic acid interactions is an area of current interest, for example, in the regulation of gene-expression. Most transcription factor proteins bind in the DNA major groove; however, we are interested in an approach using small molecules to target the minor groove to control expression by...
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abstract::In vivo and in vitro RNA splicing experiments have demonstrated that the intron splicing machineries are not interchangeable in all organisms. These differences have prevented the efficient in vivo expression of monocot genes containing introns in dicot plants and the in vitro excision of some plant introns in HeLa ce...
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abstract::Sequences of 3279 sequences of tRNA genes and tRNAs published up to December 1996 are included in the compilation. Alignment of the sequences, which is most compatible with the tRNA phylogeny and known three-dimensional structures of tRNA, is used. Sequences and references are available under http://www.uni-bayreuth. ...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::A computer program package has been made available which contains five compound programs written in FORTRAN 10 (for DECsystem-10). Program DATBAS is for storing and improving DNA sequence data, especially those obtained by the sequencing method using M13 phages. Programs NUCDAT and PROTEN are for analyzing DNA/RNA and...
journal_title:Nucleic acids research
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abstract::We have used heteroduplex analysis to investigate the sequences surrounding the germline C gamma 1 and C gamma 3 genes, and to compare them with those surrounding the C mu gene. We detected an inverted pseudogene 5' to the C gamma 3 gene and 50-65% homologous to it. A 400 bp region of the C gamma 1 and C gamma 3 3' fl...
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abstract::Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have establish...
journal_title:Nucleic acids research
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abstract::The type I insulin-like growth factor receptor (IGF-IR) is an integral component in the control of cell proliferation, differentiation and apoptosis. The IGF-IR mRNA contains an extraordinarily long (1038 nt) 5'-untranslated region (5'-UTR), and we have characterized a diverse series of proteins interacting with this ...
journal_title:Nucleic acids research
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abstract::RNA thermometers control the translation of several heat shock and virulence genes by their temperature-sensitive structural transitions. Changes in the structure and dynamics of MiniROSE RNA, which regulates translation in the temperature range of 20-45°C, were studied by site specifically replacing seven adenine res...
journal_title:Nucleic acids research
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abstract::CeR-2 RNA is one of the newly identified Caenorhabditis elegans noncoding RNAs (ncRNAs). The characterization of CeR-2 by RNomic studies has failed to classify it into any known ncRNA family. In this study, we examined the spatiotemporal expression patterns of CeR-2 to gain insight into its function. CeR-2 is expresse...
journal_title:Nucleic acids research
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doi:10.1093/nar/gkq335
更新日期:2010-09-01 00:00:00
abstract::Antimicrobial peptides (AMPs) are gaining importance as anti-infective agents. Here we describe the updated Collection of Antimicrobial Peptide (CAMP) database, available online at http://www.camp.bicnirrh.res.in/. The 3D structures of peptides are known to influence antimicrobial activity. Although there exists datab...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1157
更新日期:2014-01-01 00:00:00
abstract::Human lung epithelioid cells were treated with Benzo (a) pyrene diol epoxide (anti) in order to establish the binding and removal of covalent adducts in chromosomal components. Isolating two different classes of mononucleosomes, it was found that their DNA contained different concentrations of B(a)PDE-DNA adducts, whi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.24.9897
更新日期:1986-12-22 00:00:00
abstract::Transgenic mice suitable for the in vivo assay of suspected mutagens at the chromosome level have been constructed by stable integration of a lambda phage shuttle vector. The shuttle vector, which contains a beta-galactosidase (beta-gal) target gene, can be rescued from genomic DNA with in vitro packaging extracts. Mu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.10.3007
更新日期:1990-05-25 00:00:00
abstract::We present the results of in vitro binding studies aimed at defining the key recognition elements on the MS2 RNA translational operator (TR) essential for complex formation with coat protein. We have used chemically synthesized operators carrying modified functional groups at defined nucleotide positions, which are es...
journal_title:Nucleic acids research
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doi:10.1093/nar/23.13.2512
更新日期:1995-07-11 00:00:00
abstract::Loss-of-function in melanocortin 1 receptor (MC1R), a GS protein-coupled receptor that regulates signal transduction through cAMP and protein kinase A (PKA) in melanocytes, is a major inherited melanoma risk factor. Herein, we report a novel cAMP-mediated response for sensing and responding to UV-induced DNA damage re...
journal_title:Nucleic acids research
pub_type: 杂志文章,收录出版
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更新日期:2016-12-15 00:00:00
abstract::The intrinsic stiffness of DNA limits its ability to be bent and twisted over short lengths, but such deformations are required for gene regulation. One classic paradigm is DNA looping in the regulation of the Escherichia coli lac operon. Lac repressor protein binds simultaneously to two operator sequences flanking th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm419
更新日期:2007-01-01 00:00:00
abstract::A C-->U mutation (rdn5) in the conserved sarcin/ricin domain of yeast 25S rRNA has been shown to cause translational suppression and paromomycin resistance. It also separates the killing from the misreading effect of this antibiotic. We confirm these findings and provide in vitro evidence that rdn5 causes a 3-fold inc...
journal_title:Nucleic acids research
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doi:10.1093/nar/gkh860
更新日期:2004-10-11 00:00:00
abstract::Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, ge...
journal_title:Nucleic acids research
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更新日期:2017-01-09 00:00:00
abstract::The formation of interstrand cross-links in nucleic acids can have a strong impact on biological function of nucleic acids; therefore, many cross-linking agents have been developed for biological applications. Despite numerous studies, there remains a need for cross-linking agents that exhibit both efficiency and sele...
journal_title:Nucleic acids research
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abstract::Previously, we have shown that all class-1 polypeptide release factors (RFs) share a common glycine-glycine-glutamine (GGQ) motif, which is critical for RF activity. Here, we subjected to site-directed mutagenesis two invariant amino acids, Gln185 and Arg189, situated in the GGQ minidomain of human eRF1, followed by d...
journal_title:Nucleic acids research
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abstract::We have determined the nucleotide sequence at the 3' end of the vesicular stomatitis virus (VSV) polymerase or L gene and compared it to that obtained from a defective interfering particle (DI) RNA generated by this virus. The latter (DI 0.50) contains a large internal deletion within this gene. The deletion begins ex...
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abstract::Single-stranded DNA-binding proteins (SSBs) support DNA replication by protecting single-stranded DNA from nucleolytic attack, preventing intra-strand pairing events and playing many other regulatory roles within the replisome. Recent developments in single-molecule approaches have led to a revised picture of the repl...
journal_title:Nucleic acids research
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更新日期:2019-05-07 00:00:00
abstract::A highly polymorphic locus associated with the variable tandem repetition of a 35 bp consensus sequence was mapped to chromosome 10, band q26. Examination of leukocyte DNA from a cancer patient revealed the twenty-fold amplification of one allelic fragment of this locus, while the other allelic fragment demonstrated a...
journal_title:Nucleic acids research
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doi:10.1093/nar/14.20.7929
更新日期:1986-10-24 00:00:00
abstract::The SRPDB (signal recognition particle database) provides aligned SRP RNA and protein sequences, annotated and phylogenetically ordered. This release includes 82 SRP RNAs (including 22 bacterial and 9 archaeal homologs) and a total of 20 protein sequences representing SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72. The o...
journal_title:Nucleic acids research
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doi:10.1093/nar/22.17.3483
更新日期:1994-09-01 00:00:00
abstract::We have determined the complete nucleotide sequence of the regions of mouse ribosomal RNA transcription unit which separate mature rRNA genes. These internal transcribed spacers (ITS) are excised from rRNA precursor during ribosome biosynthesis. ITS 1, between 18S and 5.8S rRNA genes, is 999 nucleotides long. ITS 2, b...
journal_title:Nucleic acids research
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更新日期:1983-05-25 00:00:00
abstract::VA RNA(I) is a non-coding adenoviral transcript that counteracts the host cell anti-viral defenses such as immune responses mediated via PKR. We investigated potential alternate secondary structure conformations within the PKR-binding domain of VA RNA(I) using site-directed mutagenesis, RNA UV-melting analysis and enz...
journal_title:Nucleic acids research
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更新日期:2009-09-01 00:00:00
abstract::Message-specific translational regulation mechanisms shape the biogenesis of multimeric oxidative phosphorylation (OXPHOS) enzyme in mitochondria from the yeast Saccharomyces cerevisiae. These mechanisms, driven mainly by the action of mRNA-specific translational activators, help to coordinate synthesis of OXPHOS cata...
journal_title:Nucleic acids research
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更新日期:2019-06-20 00:00:00
abstract::The eel long interspersed element (LINE) UnaL2 and its partner short interspersed element (SINE) share a conserved 3' tail that is critical for their retrotransposition. The predicted secondary structure of the conserved 3' tail of UnaL2 RNA contains a stem region with a putative internal loop. Deletion of the putativ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl664
更新日期:2006-01-01 00:00:00
abstract::Accumulation of replicative intermediates of the bacteriophage phi X174 was observed in E. coli C infected cells when phage DNA methylation has been inhibited by nicotinamide or when cells were infected with a temperature-sensitive mutant in gene A. Analysis of the accumulating replicative intermediates by electron mi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.10.3483
更新日期:1977-10-01 00:00:00