Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2

Daniel W. Young, Mohammad Q. Hassan, Xiao Qing Yang, Mario Galindo, Amjad Javed, Sayyed K. Zaidi, Paul Furcinitti, David Lapointe, Martin Montecino, Jane B. Lian, Janet L. Stein, Andre J van Wijnen, Gary S. Stein

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question is how gene expression patterns are retained during mitosis to ensure the phenotype of progeny cells. We suggest that cell fate-determining transcription factors provide an epigenetic mechanism for the retention of gene expression patterns during cell division. Runx proteins are lineage-specific transcription factors that are essential for hematopoietic, neuronal, gastrointestinal, and osteogenic cell fates. Here we show that Runx2 protein is stable during cell division and remains associated with chromosomes during mitosis through sequence-specific DNA binding. Using siRNA-mediated silencing, mitotic cell synchronization, and expression profiling, we identify Runx2-regulated genes that are modulated postmitotically. Novel target genes involved in cell growth and differentiation were validated by chromatin immunoprecipitation. Importantly, we find that during mitosis, when transcription is shut down, Runx2 selectively occupies target gene promoters, and Runx2 deficiency alters mitotic histone modifications. We conclude that Runx proteins have an active role in retaining phenotype during cell division to support lineage-specific control of gene expression in progeny cells.

Original languageEnglish (US)
Pages (from-to)3189-3194
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number9
DOIs
StatePublished - Feb 27 2007
Externally publishedYes

Fingerprint

Transcription Factors
Cell Division
Core Binding Factor alpha Subunits
Gene Expression
Mitosis
Core Binding Factor Alpha 1 Subunit
Histone Code
Chromosomes
Genes
Phenotype
Chromatin Immunoprecipitation
Epigenomics
Small Interfering RNA
Cell Differentiation
Growth

Keywords

  • Cell division
  • Chromatin
  • Epigenetic control
  • Mitosis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2. / Young, Daniel W.; Hassan, Mohammad Q.; Yang, Xiao Qing; Galindo, Mario; Javed, Amjad; Zaidi, Sayyed K.; Furcinitti, Paul; Lapointe, David; Montecino, Martin; Lian, Jane B.; Stein, Janet L.; van Wijnen, Andre J; Stein, Gary S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 9, 27.02.2007, p. 3189-3194.

Research output: Contribution to journalArticle

Young, DW, Hassan, MQ, Yang, XQ, Galindo, M, Javed, A, Zaidi, SK, Furcinitti, P, Lapointe, D, Montecino, M, Lian, JB, Stein, JL, van Wijnen, AJ & Stein, GS 2007, 'Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 9, pp. 3189-3194. https://doi.org/10.1073/pnas.0611419104
Young, Daniel W. ; Hassan, Mohammad Q. ; Yang, Xiao Qing ; Galindo, Mario ; Javed, Amjad ; Zaidi, Sayyed K. ; Furcinitti, Paul ; Lapointe, David ; Montecino, Martin ; Lian, Jane B. ; Stein, Janet L. ; van Wijnen, Andre J ; Stein, Gary S. / Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 9. pp. 3189-3194.
@article{da1c8554f1c3499db53da8cc574cae3e,
title = "Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2",
abstract = "During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question is how gene expression patterns are retained during mitosis to ensure the phenotype of progeny cells. We suggest that cell fate-determining transcription factors provide an epigenetic mechanism for the retention of gene expression patterns during cell division. Runx proteins are lineage-specific transcription factors that are essential for hematopoietic, neuronal, gastrointestinal, and osteogenic cell fates. Here we show that Runx2 protein is stable during cell division and remains associated with chromosomes during mitosis through sequence-specific DNA binding. Using siRNA-mediated silencing, mitotic cell synchronization, and expression profiling, we identify Runx2-regulated genes that are modulated postmitotically. Novel target genes involved in cell growth and differentiation were validated by chromatin immunoprecipitation. Importantly, we find that during mitosis, when transcription is shut down, Runx2 selectively occupies target gene promoters, and Runx2 deficiency alters mitotic histone modifications. We conclude that Runx proteins have an active role in retaining phenotype during cell division to support lineage-specific control of gene expression in progeny cells.",
keywords = "Cell division, Chromatin, Epigenetic control, Mitosis",
author = "Young, {Daniel W.} and Hassan, {Mohammad Q.} and Yang, {Xiao Qing} and Mario Galindo and Amjad Javed and Zaidi, {Sayyed K.} and Paul Furcinitti and David Lapointe and Martin Montecino and Lian, {Jane B.} and Stein, {Janet L.} and {van Wijnen}, {Andre J} and Stein, {Gary S.}",
year = "2007",
month = "2",
day = "27",
doi = "10.1073/pnas.0611419104",
language = "English (US)",
volume = "104",
pages = "3189--3194",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9",

}

TY - JOUR

T1 - Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2

AU - Young, Daniel W.

AU - Hassan, Mohammad Q.

AU - Yang, Xiao Qing

AU - Galindo, Mario

AU - Javed, Amjad

AU - Zaidi, Sayyed K.

AU - Furcinitti, Paul

AU - Lapointe, David

AU - Montecino, Martin

AU - Lian, Jane B.

AU - Stein, Janet L.

AU - van Wijnen, Andre J

AU - Stein, Gary S.

PY - 2007/2/27

Y1 - 2007/2/27

N2 - During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question is how gene expression patterns are retained during mitosis to ensure the phenotype of progeny cells. We suggest that cell fate-determining transcription factors provide an epigenetic mechanism for the retention of gene expression patterns during cell division. Runx proteins are lineage-specific transcription factors that are essential for hematopoietic, neuronal, gastrointestinal, and osteogenic cell fates. Here we show that Runx2 protein is stable during cell division and remains associated with chromosomes during mitosis through sequence-specific DNA binding. Using siRNA-mediated silencing, mitotic cell synchronization, and expression profiling, we identify Runx2-regulated genes that are modulated postmitotically. Novel target genes involved in cell growth and differentiation were validated by chromatin immunoprecipitation. Importantly, we find that during mitosis, when transcription is shut down, Runx2 selectively occupies target gene promoters, and Runx2 deficiency alters mitotic histone modifications. We conclude that Runx proteins have an active role in retaining phenotype during cell division to support lineage-specific control of gene expression in progeny cells.

AB - During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question is how gene expression patterns are retained during mitosis to ensure the phenotype of progeny cells. We suggest that cell fate-determining transcription factors provide an epigenetic mechanism for the retention of gene expression patterns during cell division. Runx proteins are lineage-specific transcription factors that are essential for hematopoietic, neuronal, gastrointestinal, and osteogenic cell fates. Here we show that Runx2 protein is stable during cell division and remains associated with chromosomes during mitosis through sequence-specific DNA binding. Using siRNA-mediated silencing, mitotic cell synchronization, and expression profiling, we identify Runx2-regulated genes that are modulated postmitotically. Novel target genes involved in cell growth and differentiation were validated by chromatin immunoprecipitation. Importantly, we find that during mitosis, when transcription is shut down, Runx2 selectively occupies target gene promoters, and Runx2 deficiency alters mitotic histone modifications. We conclude that Runx proteins have an active role in retaining phenotype during cell division to support lineage-specific control of gene expression in progeny cells.

KW - Cell division

KW - Chromatin

KW - Epigenetic control

KW - Mitosis

UR - http://www.scopus.com/inward/record.url?scp=33847634759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847634759&partnerID=8YFLogxK

U2 - 10.1073/pnas.0611419104

DO - 10.1073/pnas.0611419104

M3 - Article

C2 - 17360627

AN - SCOPUS:33847634759

VL - 104

SP - 3189

EP - 3194

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9

ER -