HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 47, 33994-34002, November 23, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/47/33994    most recent M701847200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Evans, P. M. Articles by Liu, C. Search for Related Content PubMed PubMed Citation Articles by Evans, P. M. Articles by Liu, C. Social Bookmarking                      What's this?

Krüppel-like Factor 4 Is Acetylated by p300 and Regulates Gene Transcription via Modulation of Histone Acetylation^*

From the Sealy Center for Cancer Cell Biology, the Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555

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.

Received for publication, March 2, 2007 , and in revised form, October 1, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported in part by a Multidisciplinary Training in Cancer Research predoctoral training grant from the Sealy Center for Cancer Cell Biology and National Institutes of Health Grant T32CA117834.

² Supported by National Institutes of Health Grants R21 CA112007 and R01 DK071976. To whom correspondence should be addressed: Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1048. Tel.: 409-747-1909; Fax: 409-747-1938; E-mail: chliu{at}utmb.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K.-C. Choi, M. G. Jung, Y.-H. Lee, J. C. Yoon, S. H. Kwon, H.-B. Kang, M.-J. Kim, J.-H. Cha, Y. J. Kim, W. J. Jun, et al. Epigallocatechin-3-Gallate, a Histone Acetyltransferase Inhibitor, Inhibits EBV-Induced B Lymphocyte Transformation via Suppression of RelA Acetylation Cancer Res., January 15, 2009; 69(2): 583 - 592. [Abstract] [Full Text] [PDF]

				D. Wei, M. Kanai, Z. Jia, X. Le, and K. Xie Kruppel-like Factor 4 Induces p27Kip1 Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells Cancer Res., June 15, 2008; 68(12): 4631 - 4639. [Abstract] [Full Text] [PDF]

				V. V. Lunyak and M. G. Rosenfeld Epigenetic regulation of stem cell fate Hum. Mol. Genet., April 15, 2008; 17(R1): R28 - R36. [Abstract] [Full Text] [PDF]

				M. Stojkovic and D. G. Phinney Reprogramming Battle: Egg Vs. Virus Stem Cells, January 1, 2008; 26(1): 1 - 2. [Full Text] [PDF]