Time-dependent c-Myc transactomes mapped by array-based nuclear run-on reveal transcriptional modules in human B cells

Jinshui Fan, Karen Zeller, Yu Chi Chen, Tonya Watkins, Kathleen C. Barnes, Kevin G. Becker, Chi V. Dang, Chris Cheadle

Research output: Contribution to journalArticle

Abstract

Background: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome"). Methodology/Principal Findings: We developed a method to measure nascent nuclear gene transcription with an Arraybased Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493- 6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/ HIF motifs. Conclusions/Significance: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.

Original languageEnglish (US)
Article numbere9691
JournalPLoS One
Volume5
Issue number3
DOIs
StatePublished - 2010

Fingerprint

Gene Regulatory Networks
B-lymphocytes
myc Genes
B-Lymphocytes
Genes
Cells
Transcription
Transcription Factors
Binding Sites
transcription (genetics)
genes
Gene expression
Chromatin Immunoprecipitation
Chromosome Mapping
binding sites
Transcriptome
transcription factors
gene expression
Gene Expression
Microarrays

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Time-dependent c-Myc transactomes mapped by array-based nuclear run-on reveal transcriptional modules in human B cells. / Fan, Jinshui; Zeller, Karen; Chen, Yu Chi; Watkins, Tonya; Barnes, Kathleen C.; Becker, Kevin G.; Dang, Chi V.; Cheadle, Chris.

In: PLoS One, Vol. 5, No. 3, e9691, 2010.

Research output: Contribution to journalArticle

Fan, Jinshui ; Zeller, Karen ; Chen, Yu Chi ; Watkins, Tonya ; Barnes, Kathleen C. ; Becker, Kevin G. ; Dang, Chi V. ; Cheadle, Chris. / Time-dependent c-Myc transactomes mapped by array-based nuclear run-on reveal transcriptional modules in human B cells. In: PLoS One. 2010 ; Vol. 5, No. 3.
@article{a22714fa11a24b28a5d8932ada38ccbe,
title = "Time-dependent c-Myc transactomes mapped by array-based nuclear run-on reveal transcriptional modules in human B cells",
abstract = "Background: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined {"}transactome{"}). Methodology/Principal Findings: We developed a method to measure nascent nuclear gene transcription with an Arraybased Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493- 6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/ HIF motifs. Conclusions/Significance: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.",
author = "Jinshui Fan and Karen Zeller and Chen, {Yu Chi} and Tonya Watkins and Barnes, {Kathleen C.} and Becker, {Kevin G.} and Dang, {Chi V.} and Chris Cheadle",
year = "2010",
doi = "10.1371/journal.pone.0009691",
language = "English (US)",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Time-dependent c-Myc transactomes mapped by array-based nuclear run-on reveal transcriptional modules in human B cells

AU - Fan, Jinshui

AU - Zeller, Karen

AU - Chen, Yu Chi

AU - Watkins, Tonya

AU - Barnes, Kathleen C.

AU - Becker, Kevin G.

AU - Dang, Chi V.

AU - Cheadle, Chris

PY - 2010

Y1 - 2010

N2 - Background: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome"). Methodology/Principal Findings: We developed a method to measure nascent nuclear gene transcription with an Arraybased Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493- 6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/ HIF motifs. Conclusions/Significance: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.

AB - Background: The definition of transcriptional networks through measurements of changes in gene expression profiles and mapping of transcription factor binding sites is limited by the moderate overlap between binding and gene expression changes and the inability to directly measure global nuclear transcription (coined "transactome"). Methodology/Principal Findings: We developed a method to measure nascent nuclear gene transcription with an Arraybased Nuclear Run-On (ANRO) assay using commercial microarray platforms. This strategy provides the missing component, the transactome, to fully map transcriptional networks. ANRO measurements in an inducible c-Myc expressing human P493- 6 B cell model reveals time-dependent waves of transcription, with a transactome early after c-Myc induction that does not persist at a late, steady-state phase, when genes that are regulated by c-Myc and E2F predominate. Gene set matrix analysis further uncovers functionally related groups of genes putatively regulated by waves of transcription factor motifs following Myc induction, starting with AP1 and CREB that are followed by EGR1, NFkB and STAT, and ending with E2F, Myc and ARNT/ HIF motifs. Conclusions/Significance: By coupling ANRO with previous global mapping of c-Myc binding sites by chromatin immunoprecipitation (ChIP) in P493-6 cells, we define a set of transcriptionally regulated direct c-Myc target genes and pave the way for the use of ANRO to comprehensively map any transcriptional network.

UR - http://www.scopus.com/inward/record.url?scp=79551675788&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551675788&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0009691

DO - 10.1371/journal.pone.0009691

M3 - Article

C2 - 20300622

AN - SCOPUS:79551675788

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e9691

ER -