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Motif module map reveals enforcement of aging by continual NF-kappaB activity.

Publication ,  Journal Article
Adler, AS; Sinha, S; Kawahara, TLA; Zhang, JY; Segal, E; Chang, HY
Published in: Genes Dev
December 15, 2007

Aging is characterized by specific alterations in gene expression, but their underlying mechanisms and functional consequences are not well understood. Here we develop a systematic approach to identify combinatorial cis-regulatory motifs that drive age-dependent gene expression across different tissues and organisms. Integrated analysis of 365 microarrays spanning nine tissue types predicted fourteen motifs as major regulators of age-dependent gene expression in human and mouse. The motif most strongly associated with aging was that of the transcription factor NF-kappaB. Inducible genetic blockade of NF-kappaB for 2 wk in the epidermis of chronologically aged mice reverted the tissue characteristics and global gene expression programs to those of young mice. Age-specific NF-kappaB blockade and orthogonal cell cycle interventions revealed that NF-kappaB controls cell cycle exit and gene expression signature of aging in parallel but not sequential pathways. These results identify a conserved network of regulatory pathways underlying mammalian aging and show that NF-kappaB is continually required to enforce many features of aging in a tissue-specific manner.

Duke Scholars

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

December 15, 2007

Volume

21

Issue

24

Start / End Page

3244 / 3257

Location

United States

Related Subject Headings

  • Phenotype
  • NF-kappa B
  • Molecular Sequence Data
  • Mice
  • Immunohistochemistry
  • Humans
  • Gene Expression Regulation
  • Electrophoretic Mobility Shift Assay
  • Developmental Biology
  • Animals
 

Citation

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Chicago
ICMJE
MLA
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Adler, A. S., Sinha, S., Kawahara, T. L. A., Zhang, J. Y., Segal, E., & Chang, H. Y. (2007). Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev, 21(24), 3244–3257. https://doi.org/10.1101/gad.1588507
Adler, Adam S., Saurabh Sinha, Tiara L. A. Kawahara, Jennifer Y. Zhang, Eran Segal, and Howard Y. Chang. “Motif module map reveals enforcement of aging by continual NF-kappaB activity.Genes Dev 21, no. 24 (December 15, 2007): 3244–57. https://doi.org/10.1101/gad.1588507.
Adler AS, Sinha S, Kawahara TLA, Zhang JY, Segal E, Chang HY. Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev. 2007 Dec 15;21(24):3244–57.
Adler, Adam S., et al. “Motif module map reveals enforcement of aging by continual NF-kappaB activity.Genes Dev, vol. 21, no. 24, Dec. 2007, pp. 3244–57. Pubmed, doi:10.1101/gad.1588507.
Adler AS, Sinha S, Kawahara TLA, Zhang JY, Segal E, Chang HY. Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev. 2007 Dec 15;21(24):3244–3257.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

December 15, 2007

Volume

21

Issue

24

Start / End Page

3244 / 3257

Location

United States

Related Subject Headings

  • Phenotype
  • NF-kappa B
  • Molecular Sequence Data
  • Mice
  • Immunohistochemistry
  • Humans
  • Gene Expression Regulation
  • Electrophoretic Mobility Shift Assay
  • Developmental Biology
  • Animals