Acetylation of histones associated with the p21WAF1/CIP1 gene by butyrate is not sufficient for p21WAF1/CIP1 gene transcription in human colorectal adenocarcinoma cells
Open Access
- 22 December 2003
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 109 (2) , 207-213
- https://doi.org/10.1002/ijc.11697
Abstract
Butyric acid is well recognized as a histone deacetylase (HDAC) inhibitor, and changes in histone acetylation are thought to alter gene expression. The mechanism by which sodium butyrate (NaB) induces p21WAF1/CIP1, a critical gene involved in the antiproliferative effect of NaB, was studied at the chromatin level. Using chromatin immunoprecipitation (ChIP) assay, acetylation of histone H3 was observed at the proximal region of the promoter within 30 min of NaB exposure and this extended to the distal region within 2 hr. By contrast, histone H4 was acetylated both at the proximal and the distal regions of the promoter within 30 min. NaB did not influence other histone modifications. NaB stimulated recruitment of the transcription factors ZBP89 and Sp1 as well as GCN5, but did not influence recruitment of Sp3, HDAC1, p300, or CBP. As recruitment of HDAC1 to the promoter appeared not to account for NaB-induced changes in histone acetylation, we aimed to influence HDAC activity by altering its phosphorylation status. The kinase inhibitor, H7, suppressed p21WAF1/CIP1 mRNA in both the absence and the presence of NaB without influencing the butyrate-induced hyperacetylation of H3 and H4 associated with the p21WAF1/CIP1 promoter. These results suggest that acetylation of histones at the p21WAF1/CIP1 promoter is not sufficient for NaB to exert antiproliferative effects via transcription of the p21WAF1/CIP1 gene. Induction of p21WAF1/CIP1 transcription by the phosphatase inhibitor, okadaic acid, in the absence of changes in association of acetylated histones with the p21WAF1/CIP1 promoter provides further evidence of the importance of phosphorylation to p21WAF1/CIP1 transcription.Keywords
This publication has 51 references indexed in Scilit:
- Regulation of TATA-Binding Protein Binding by the SAGA Complex and the Nhp6 High-Mobility Group ProteinMolecular and Cellular Biology, 2003
- Induction and superinduction of growth arrest and DNA damage gene 45 (GADD45) α and β messenger RNAs by histone deacetylase inhibitors trichostatin A (TSA) and butyrate in SW620 human colon carcinoma cellsCancer Letters, 2002
- Inhibition of histone acetyltransferase function of p300 by PKCδBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2002
- Cell‐line specific chromatin acetylation at the Sox10–Pax3 enhancer site modulates the RET proto‐oncogene expressionFEBS Letters, 2002
- Activation of p21WAF1/Cip1 Transcription through Sp1 Sites by Histone Deacetylase Inhibitor ApicidinJournal of Biological Chemistry, 2001
- Mammalian Histone Deacetylase 1 Protein Is Posttranslationally Modified by PhosphorylationBiochemical and Biophysical Research Communications, 2001
- Sp1 and Sp3 activate p21 (WAF1/CIP1) gene transcription in the Caco-2 colon adenocarcinoma cell lineOncogene, 2000
- Inhibition by Deacetylase Inhibitors of IL-1-Dependent Induction of Haptoglobin Involves CCAAT/Enhancer-Binding Protein Isoforms in Intestinal Epithelial CellsBiochemical and Biophysical Research Communications, 2000
- Transcription Factor ZBP-89 Cooperates with Histone Acetyltransferase p300 during Butyrate Activation of p21 Transcription in Human CellsPublished by Elsevier ,2000
- Increased Intestinal Bak Expression Results in ApoptosisBiochemical and Biophysical Research Communications, 1996