The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma

Olivier van Beekum, Arjan B Brenkman, Lars Grøntved, Nicole Hamers, Niels J F van den Broek, Ruud Berger, Susanne Mandrup, Eric Kalkhoven

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism in adipocytes, by regulating their differentiation, maintenance, and function. The transcriptional activity of PPARgamma is dictated by the set of proteins with which this nuclear receptor interacts under specific conditions. Here we identify the HIV-1 Tat-interacting protein 60 (Tip60) as a novel positive regulator of PPARgamma transcriptional activity. Using tandem mass spectrometry, we found that PPARgamma and the acetyltransferase Tip60 interact in cells, and through use of chimeric proteins, we established that coactivation by Tip60 critically depends on the N-terminal activation function 1 of PPARgamma, a domain involved in isotype-specific gene expression and adipogenesis. Chromatin immunoprecipitation experiments showed that the endogenous Tip60 protein is recruited to PPARgamma target genes in mature 3T3-L1 adipocytes but not in preadipocytes, indicating that Tip60 requires PPARgamma for its recruitment to PPARgamma target genes. Importantly, we show that in common with disruption of PPARgamma function, small interfering RNA-mediated reduction of Tip60 protein impairs differentiation of 3T3-L1 preadipocytes. Taken together, these findings qualify the acetyltransferase Tip60 as a novel adipogenic factor.
Original languageEnglish
JournalEndocrinology
Volume149
Issue number4
Pages (from-to)1840-1849
Number of pages9
ISSN0013-7227
DOIs
Publication statusPublished - 2008

Fingerprint

PPAR gamma
Adipocytes
Proteins
Adipogenesis
Chromatin Immunoprecipitation
Cytoplasmic and Nuclear Receptors
Tandem Mass Spectrometry
Lipid Metabolism
Small Interfering RNA
HIV-1
Maintenance

Keywords

  • 3T3-L1 Cells
  • Adipogenesis
  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Histone Acetyltransferases
  • Humans
  • Mice
  • Molecular Sequence Data
  • PPAR gamma
  • Protein Structure, Tertiary
  • Transcription, Genetic

Cite this

van Beekum, O., Brenkman, A. B., Grøntved, L., Hamers, N., van den Broek, N. J. F., Berger, R., ... Kalkhoven, E. (2008). The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma. Endocrinology, 149(4), 1840-1849. https://doi.org/10.1210/en.2007-0977
van Beekum, Olivier ; Brenkman, Arjan B ; Grøntved, Lars ; Hamers, Nicole ; van den Broek, Niels J F ; Berger, Ruud ; Mandrup, Susanne ; Kalkhoven, Eric. / The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma. In: Endocrinology. 2008 ; Vol. 149, No. 4. pp. 1840-1849.
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abstract = "The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism in adipocytes, by regulating their differentiation, maintenance, and function. The transcriptional activity of PPARgamma is dictated by the set of proteins with which this nuclear receptor interacts under specific conditions. Here we identify the HIV-1 Tat-interacting protein 60 (Tip60) as a novel positive regulator of PPARgamma transcriptional activity. Using tandem mass spectrometry, we found that PPARgamma and the acetyltransferase Tip60 interact in cells, and through use of chimeric proteins, we established that coactivation by Tip60 critically depends on the N-terminal activation function 1 of PPARgamma, a domain involved in isotype-specific gene expression and adipogenesis. Chromatin immunoprecipitation experiments showed that the endogenous Tip60 protein is recruited to PPARgamma target genes in mature 3T3-L1 adipocytes but not in preadipocytes, indicating that Tip60 requires PPARgamma for its recruitment to PPARgamma target genes. Importantly, we show that in common with disruption of PPARgamma function, small interfering RNA-mediated reduction of Tip60 protein impairs differentiation of 3T3-L1 preadipocytes. Taken together, these findings qualify the acetyltransferase Tip60 as a novel adipogenic factor.",
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The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma. / van Beekum, Olivier; Brenkman, Arjan B; Grøntved, Lars; Hamers, Nicole; van den Broek, Niels J F; Berger, Ruud; Mandrup, Susanne; Kalkhoven, Eric.

In: Endocrinology, Vol. 149, No. 4, 2008, p. 1840-1849.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma

AU - van Beekum, Olivier

AU - Brenkman, Arjan B

AU - Grøntved, Lars

AU - Hamers, Nicole

AU - van den Broek, Niels J F

AU - Berger, Ruud

AU - Mandrup, Susanne

AU - Kalkhoven, Eric

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AB - The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism in adipocytes, by regulating their differentiation, maintenance, and function. The transcriptional activity of PPARgamma is dictated by the set of proteins with which this nuclear receptor interacts under specific conditions. Here we identify the HIV-1 Tat-interacting protein 60 (Tip60) as a novel positive regulator of PPARgamma transcriptional activity. Using tandem mass spectrometry, we found that PPARgamma and the acetyltransferase Tip60 interact in cells, and through use of chimeric proteins, we established that coactivation by Tip60 critically depends on the N-terminal activation function 1 of PPARgamma, a domain involved in isotype-specific gene expression and adipogenesis. Chromatin immunoprecipitation experiments showed that the endogenous Tip60 protein is recruited to PPARgamma target genes in mature 3T3-L1 adipocytes but not in preadipocytes, indicating that Tip60 requires PPARgamma for its recruitment to PPARgamma target genes. Importantly, we show that in common with disruption of PPARgamma function, small interfering RNA-mediated reduction of Tip60 protein impairs differentiation of 3T3-L1 preadipocytes. Taken together, these findings qualify the acetyltransferase Tip60 as a novel adipogenic factor.

KW - 3T3-L1 Cells

KW - Adipogenesis

KW - Amino Acid Sequence

KW - Animals

KW - Cell Line, Tumor

KW - Histone Acetyltransferases

KW - Humans

KW - Mice

KW - Molecular Sequence Data

KW - PPAR gamma

KW - Protein Structure, Tertiary

KW - Transcription, Genetic

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DO - 10.1210/en.2007-0977

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JO - Endocrinology

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SN - 0013-7227

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ER -