Transcript Dynamics of Proinflammatory Genes Revealed by Sequence Analysis of Subcellular RNA Fractions

被引：345

作者：

Bhatt, Dev M. ^{[1
]}

Pandya-Jones, Amy ^{[1
,2
]}

Tong, Ann-Jay ^{[1
,3
]}

Barozzi, Iros ^{[4
]}

Lissner, Michelle M. ^{[1
]}

Natoli, Gioacchino ^{[4
]}

Black, Douglas L. ^{[1
,2
,3
]}

Smale, Stephen T. ^{[1
,3
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[4] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy

来源：

CELL | 2012年 / 150卷 / 02期

关键词：

MESSENGER-RNA; POLYMERASE-II; INFLAMMATORY RESPONSE; MAMMALIAN-CELLS; SEQ; EXPRESSION; ELONGATION; INDUCTION; MEDIATORS; MOLECULES;

D O I：

10.1016/j.cell.2012.05.043

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Macrophages respond to inflammatory stimuli by modulating the expression of hundreds of genes in a defined temporal cascade, with diverse transcriptional and posttranscriptional mechanisms contributing to the regulatory network. We examined proinflammatory gene regulation in activated macrophages by performing RNA-seq with fractionated chromatin-associated, nucleoplasmic, and cytoplasmic transcripts. This methodological approach allowed us to separate the synthesis of nascent transcripts from transcript processing and the accumulation of mature mRNAs. In addition to documenting the subcellular locations of coding and noncoding transcripts, the results provide a high-resolution view of the relationship between defined promoter and chromatin properties and the temporal regulation of diverse classes of coexpressed genes. The data also reveal a striking accumulation of full-length yet incompletely spliced transcripts in the chromatin fraction, suggesting that splicing often occurs after transcription has been completed, with transcripts retained on the chromatin until fully spliced.

引用

页码：279 / 290

页数：12

共 43 条

[1] Immediate mediators of the inflammatory response are poised for gene activation through RNA polymerase II stalling [J].

Adelman, Karen ;

Kennedy, Megan A. ;

Nechaev, Sergei ;

Gilchrist, Daniel A. ;

Muse, Ginger W. ;

Chinenov, Yurii ;

Rogatsky, Inez .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (43) :18207-18212

[2] Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses [J].

Amit, Ido ;

Garber, Manuel ;

Chevrier, Nicolas ;

Leite, Ana Paula ;

Donner, Yoni ;

Eisenhaure, Thomas ;

Guttman, Mitchell ;

Grenier, Jennifer K. ;

Li, Weibo ;

Zuk, Or ;

Schubert, Lisa A. ;

Birditt, Brian ;

Shay, Tal ;

Goren, Alon ;

Zhang, Xiaolan ;

Smith, Zachary ;

Deering, Raquel ;

McDonald, Rebecca C. ;

Cabili, Moran ;

Bernstein, Bradley E. ;

Rinn, John L. ;

Meissner, Alex ;

Root, David E. ;

Hacohen, Nir ;

Regev, Aviv .

SCIENCE, 2009, 326 (5950) :257-263

[3] The In Vivo Kinetics of RNA Polymerase II Elongation during Co-Transcriptional Splicing [J].

Brody, Yehuda ;

Neufeld, Noa ;

Bieberstein, Nicole ;

Causse, Sebastien Z. ;

Boehnlein, Eva-Maria ;

Neugebauer, Karla M. ;

Darzacq, Xavier ;

Shav-Tal, Yaron .

PLOS BIOLOGY, 2011, 9 (01)

[4] IDENTIFICATION OF A COMMON NUCLEOTIDE-SEQUENCE IN THE 3'-UNTRANSLATED REGION OF MESSENGER-RNA MOLECULES SPECIFYING INFLAMMATORY MEDIATORS [J].

CAPUT, D ;

BEUTLER, B ;

HARTOG, K ;

THAYER, R ;

BROWNSHIMER, S ;

CERAMI, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (06) :1670-1674

[5] Hierarchical regulation of mRNA partitioning between the cytoplasm and the endoplasmic reticulum of mammalian cells [J].

Chen, Qiang ;

Jagannathan, Sujatha ;

Reid, David W. ;

Zheng, Tianli ;

Nicchitta, Christopher V. .

MOLECULAR BIOLOGY OF THE CELL, 2011, 22 (14) :2646-2658

[6] Nascent transcript sequencing visualizes transcription at nucleotide resolution [J].

Churchman, L. Stirling ;

Weissman, Jonathan S. .

NATURE, 2011, 469 (7330) :368-+

[7] Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters [J].

Core, Leighton J. ;

Waterfall, Joshua J. ;

Lis, John T. .

SCIENCE, 2008, 322 (5909) :1845-1848

[8] Jmjd3 contributes to the control of gene expression in LPS-activated macrophages [J].

De Santa, Francesca ;

Narang, Vipin ;

Yap, Zhei Hwee ;

Tusi, Betsabeh Khoramian ;

Burgold, Thomas ;

Austenaa, Liv ;

Bucci, Gabriele ;

Caganova, Marieta ;

Notarbartolo, Samuele ;

Casola, Stefano ;

Testa, Giuseppe ;

Sung, Wing-Kin ;

Wei, Chia-Lin ;

Natoli, Gioacchino .

EMBO JOURNAL, 2009, 28 (21) :3341-3352

[9] Exon tethering in transcription by RNA polymerase II [J].

Dye, MJ ;

Gromak, N ;

Proudfoot, NJ .

MOLECULAR CELL, 2006, 21 (06) :849-859

[10] Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes [J].

Escoubet-Lozach, Laure ;

Benner, Christopher ;

Kaikkonen, Minna U. ;

Lozach, Jean ;

Heinz, Sven ;

Spann, Nathan J. ;

Crotti, Andrea ;

Stender, Josh ;

Ghisletti, Serena ;

Reichart, Donna ;

Cheng, Christine S. ;

Luna, Rosa ;

Ludka, Colleen ;

Sasik, Roman ;

Garcia-Bassets, Ivan ;

Hoffmann, Alexander ;

Subramaniam, Shankar ;

Hardiman, Gary ;

Rosenfeld, Michael G. ;

Glass, Christopher K. .

PLOS GENETICS, 2011, 7 (12)

← 1 2 3 4 5 →