Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression

Hye Sook Kwon, Boli Huang, Nam Ho Jeoung, Pengfei Wu, Calvin N. Steussy, Robert Harris

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor α (RXRα) and retinoic acid receptor α (RARα) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRα/RARα/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRα/RARα/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1759
Issue number3-4
DOIs
StatePublished - Mar 2006

Fingerprint

trichostatin A
Histone Deacetylase Inhibitors
Tretinoin
Gene expression
CCAAT-Binding Factor
Retinoid X Receptors
Gene Expression
Retinoic Acid Receptors
Transcription
Acetylation
Genes
Response Elements
Histones
Transcriptional Activation
Gluconeogenesis
Chromatin Immunoprecipitation
Starvation
Chromatin
Blood Glucose
pyruvate dehydrogenase kinase 4

Keywords

  • Histone
  • Histone acetylation
  • Histone deacetylase
  • Human
  • Pyruvate dehydrogenase
  • Pyruvate dehydrogenase kinase
  • Retinoic acid
  • Retinoic acid receptor
  • Retinoid X receptor
  • Trichostatin A

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics

Cite this

Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression. / Kwon, Hye Sook; Huang, Boli; Ho Jeoung, Nam; Wu, Pengfei; Steussy, Calvin N.; Harris, Robert.

In: Biochimica et Biophysica Acta - Gene Structure and Expression, Vol. 1759, No. 3-4, 03.2006, p. 141-151.

Research output: Contribution to journalArticle

@article{751ace0f9f004bd8ae0b9a7fa6e38709,
title = "Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression",
abstract = "Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor α (RXRα) and retinoic acid receptor α (RARα) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRα/RARα/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRα/RARα/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.",
keywords = "Histone, Histone acetylation, Histone deacetylase, Human, Pyruvate dehydrogenase, Pyruvate dehydrogenase kinase, Retinoic acid, Retinoic acid receptor, Retinoid X receptor, Trichostatin A",
author = "Kwon, {Hye Sook} and Boli Huang and {Ho Jeoung}, Nam and Pengfei Wu and Steussy, {Calvin N.} and Robert Harris",
year = "2006",
month = "3",
doi = "10.1016/j.bbaexp.2006.04.005",
language = "English",
volume = "1759",
pages = "141--151",
journal = "Biochimica et Biophysica Acta - Gene Structure and Expression",
issn = "0167-4781",
publisher = "Elsevier BV",
number = "3-4",

}

TY - JOUR

T1 - Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression

AU - Kwon, Hye Sook

AU - Huang, Boli

AU - Ho Jeoung, Nam

AU - Wu, Pengfei

AU - Steussy, Calvin N.

AU - Harris, Robert

PY - 2006/3

Y1 - 2006/3

N2 - Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor α (RXRα) and retinoic acid receptor α (RARα) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRα/RARα/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRα/RARα/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

AB - Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor α (RXRα) and retinoic acid receptor α (RARα) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRα/RARα/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRα/RARα/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

KW - Histone

KW - Histone acetylation

KW - Histone deacetylase

KW - Human

KW - Pyruvate dehydrogenase

KW - Pyruvate dehydrogenase kinase

KW - Retinoic acid

KW - Retinoic acid receptor

KW - Retinoid X receptor

KW - Trichostatin A

UR - http://www.scopus.com/inward/record.url?scp=33744548663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744548663&partnerID=8YFLogxK

U2 - 10.1016/j.bbaexp.2006.04.005

DO - 10.1016/j.bbaexp.2006.04.005

M3 - Article

C2 - 16757381

AN - SCOPUS:33744548663

VL - 1759

SP - 141

EP - 151

JO - Biochimica et Biophysica Acta - Gene Structure and Expression

JF - Biochimica et Biophysica Acta - Gene Structure and Expression

SN - 0167-4781

IS - 3-4

ER -