Selective modulation of promoter recruitment and transcriptional activity of PPARγ

Dorothy D. Sears; Albert Hsiao; Jachelle M. Ofrecio; Justin Chapman; Weimin He; Jerrold M. Olefsky

doi:10.1016/j.bbrc.2007.10.057

Selective modulation of promoter recruitment and transcriptional activity of PPARγ

Dorothy D. Sears, Albert Hsiao, Jachelle M. Ofrecio, Justin Chapman, Weimin He, Jerrold M. Olefsky

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor regulated by the insulin-sensitizing thiazolidinediones (TZDs). We studied selective modulation of endogenous genes by PPARγ ligands using microarray, RNA expression kinetics, and chromatin immunoprecipitation (ChIP) in 3T3-L1 adipocytes. We found over 300 genes that were significantly regulated the TZDs pioglitazone, rosiglitazone, and troglitazone. TZD-mediated expression profiles were unique but overlapping. Ninety-one genes were commonly regulated by all three ligands. TZD time course and dose-response studies revealed gene- and TZD-specific expression kinetics. PEPCK expression was induced rapidly but PDK4 expression was induced gradually. Troglitazone EC₅₀ values for PEPCK, PDK4, and RGS2 regulation were greater than those for pioglitazone and rosiglitazone. TZDs differentially induced histone acetylation of and PPARγ recruitment to target gene promoters. Selective modulation of PPARγ by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes.

Original language	English (US)
Pages (from-to)	515-521
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	364
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2007.10.057
State	Published - Dec 21 2007
Externally published	Yes

Keywords

3T3-L1 adipocytes
Chromatin immunoprecipitation
Microarray
Selective peroxisome proliferator-activated receptor modulator (SPPARM)
Thiazolidinedione (TZD)
Transcription

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2007.10.057

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title = "Selective modulation of promoter recruitment and transcriptional activity of PPARγ",

abstract = "Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor regulated by the insulin-sensitizing thiazolidinediones (TZDs). We studied selective modulation of endogenous genes by PPARγ ligands using microarray, RNA expression kinetics, and chromatin immunoprecipitation (ChIP) in 3T3-L1 adipocytes. We found over 300 genes that were significantly regulated the TZDs pioglitazone, rosiglitazone, and troglitazone. TZD-mediated expression profiles were unique but overlapping. Ninety-one genes were commonly regulated by all three ligands. TZD time course and dose-response studies revealed gene- and TZD-specific expression kinetics. PEPCK expression was induced rapidly but PDK4 expression was induced gradually. Troglitazone EC50 values for PEPCK, PDK4, and RGS2 regulation were greater than those for pioglitazone and rosiglitazone. TZDs differentially induced histone acetylation of and PPARγ recruitment to target gene promoters. Selective modulation of PPARγ by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes.",

keywords = "3T3-L1 adipocytes, Chromatin immunoprecipitation, Microarray, Selective peroxisome proliferator-activated receptor modulator (SPPARM), Thiazolidinedione (TZD), Transcription",

author = "Sears, {Dorothy D.} and Albert Hsiao and Ofrecio, {Jachelle M.} and Justin Chapman and Weimin He and Olefsky, {Jerrold M.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health, NIDDK KO1-DK62025 (DDS), NIDDK RO1-DK33651 (J.M. Olefsky), and by the University of California, Discovery Program Project #bio03-10383 (BioStar) with matching funds from Pfizer, Inc. (J.M. Olefsky). J.M. Olefsky is a consultant for Pfizer, Inc. ",

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doi = "10.1016/j.bbrc.2007.10.057",

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T1 - Selective modulation of promoter recruitment and transcriptional activity of PPARγ

AU - Sears, Dorothy D.

AU - Hsiao, Albert

AU - Ofrecio, Jachelle M.

AU - Chapman, Justin

AU - He, Weimin

AU - Olefsky, Jerrold M.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health, NIDDK KO1-DK62025 (DDS), NIDDK RO1-DK33651 (J.M. Olefsky), and by the University of California, Discovery Program Project #bio03-10383 (BioStar) with matching funds from Pfizer, Inc. (J.M. Olefsky). J.M. Olefsky is a consultant for Pfizer, Inc.

PY - 2007/12/21

Y1 - 2007/12/21

N2 - Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor regulated by the insulin-sensitizing thiazolidinediones (TZDs). We studied selective modulation of endogenous genes by PPARγ ligands using microarray, RNA expression kinetics, and chromatin immunoprecipitation (ChIP) in 3T3-L1 adipocytes. We found over 300 genes that were significantly regulated the TZDs pioglitazone, rosiglitazone, and troglitazone. TZD-mediated expression profiles were unique but overlapping. Ninety-one genes were commonly regulated by all three ligands. TZD time course and dose-response studies revealed gene- and TZD-specific expression kinetics. PEPCK expression was induced rapidly but PDK4 expression was induced gradually. Troglitazone EC50 values for PEPCK, PDK4, and RGS2 regulation were greater than those for pioglitazone and rosiglitazone. TZDs differentially induced histone acetylation of and PPARγ recruitment to target gene promoters. Selective modulation of PPARγ by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes.

AB - Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor regulated by the insulin-sensitizing thiazolidinediones (TZDs). We studied selective modulation of endogenous genes by PPARγ ligands using microarray, RNA expression kinetics, and chromatin immunoprecipitation (ChIP) in 3T3-L1 adipocytes. We found over 300 genes that were significantly regulated the TZDs pioglitazone, rosiglitazone, and troglitazone. TZD-mediated expression profiles were unique but overlapping. Ninety-one genes were commonly regulated by all three ligands. TZD time course and dose-response studies revealed gene- and TZD-specific expression kinetics. PEPCK expression was induced rapidly but PDK4 expression was induced gradually. Troglitazone EC50 values for PEPCK, PDK4, and RGS2 regulation were greater than those for pioglitazone and rosiglitazone. TZDs differentially induced histone acetylation of and PPARγ recruitment to target gene promoters. Selective modulation of PPARγ by TZDs resulted in distinct expression profiles and transcription kinetics which may be due to differential promoter activation and chromatin remodeling of target genes.

KW - 3T3-L1 adipocytes

KW - Chromatin immunoprecipitation

KW - Microarray

KW - Selective peroxisome proliferator-activated receptor modulator (SPPARM)

KW - Thiazolidinedione (TZD)

KW - Transcription

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SN - 0006-291X

VL - 364

SP - 515

EP - 521

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Selective modulation of promoter recruitment and transcriptional activity of PPARγ

Abstract

Keywords

ASJC Scopus subject areas

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