Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation

Paul M. Evans, Wen Zhang, Xi Chen, Jun Yang, Kishor K. Bhakat, Chunming Liu

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Colon cancer is the second leading cause of cancer death in the United States. Krüppel-like factor 4 (KLF4) is a transcription factor involved in both proliferation and differentiation in the colon. It is down-regulated in both mouse and human colonic adenomas and has been implicated as a tumor suppressor in the gut, whereas in breast cancer, KLF4 is an oncogene. KLF4 is also involved in reprogramming differentiated cells into pluripotent stem cells. KLF4 can act as a transcriptional activator or repressor, but the underlying mechanisms are poorly understood. We found that p300, a CREB-binding protein-related protein, interacts with KLF4 both in vitro and in vivo and activates transcription. We further made the novel observation that endogenous KLF4 is acetylated by p300/CBP in vivo and that mutations of the acetylated lysines resulted in a decreased ability of KLF4 to activate target genes, suggesting that acetylation is important for KLF4-mediated transactivation. Furthermore, we found that KLF4 differentially modulates histone H4 acetylation at the promoters of target genes. Co-transfection of KLF4 and HDAC3 resulted in a synergistic repression of a cyclin B1 reporter construct. Our results suggest that KLF4 might function as an activator or repressor of transcription depending on whether it interacts with co-activators such as p300 and CREB-binding protein or co-repressors such as HDAC3.

Original languageEnglish (US)
Pages (from-to)33994-34002
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number47
DOIs
StatePublished - Nov 23 2007

Fingerprint

CREB-Binding Protein
Acetylation
Transcription
Histones
Genes
Modulation
Activator Appliances
Cyclin B1
Co-Repressor Proteins
Pluripotent Stem Cells
Stem cells
Oncogenes
Adenoma
Colonic Neoplasms
Transcriptional Activation
Lysine
Transfection
Tumors
Cause of Death
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation. / Evans, Paul M.; Zhang, Wen; Chen, Xi; Yang, Jun; Bhakat, Kishor K.; Liu, Chunming.

In: Journal of Biological Chemistry, Vol. 282, No. 47, 23.11.2007, p. 33994-34002.

Research output: Contribution to journalArticle

Evans, Paul M. ; Zhang, Wen ; Chen, Xi ; Yang, Jun ; Bhakat, Kishor K. ; Liu, Chunming. / Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 47. pp. 33994-34002.
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