Skip to main content
Article thumbnail
Location of Repository

The Role of p300 Histone Acetyltransferase in UV-Induced Histone Modifications and MMP-1 Gene Transcription

By Min-Kyoung Kim, Jung-Min Shin, Hee Chul Eun and Jin Ho Chung


Matrix metalloproteinase (MMP)-1 promotes ultraviolet (UV)-triggered long-term detrimental effects such as cancer formation and premature skin aging. Although histone modifications may play a crucial role in the transcriptional regulation of MMP-1, the relationship between UV-induced histone modification and MMP-1 expression is not completely understood. Here, we identify regulators of histone acetylation that may link UV-mediated DNA damage and MMP-1 induction by UV in cultured human dermal fibroblasts (HDFs) in vitro. UV irradiation of HDFs induced MMP-1 expression and increased the level of phosphorylation of H2AX (γ-H2AX), p53 and the acetylation of histone H3 (acetyl-H3). Total histone deacetylase (HDAC) enzymatic activity was decreased by UV irradiation, while histone acetyltransferase (HAT) activity was increased. Suppression of p300 histone acetyltransferase (p300HAT) activity by the p300HAT inhibitor anacardic acid (AA) or by down-regulation of p300 by siRNA prevented UV-induced MMP-1 expression and inhibited UV-enhanced γ-H2AX, p53 level, and acetyl-H3. Using chromatin immunoprecipitation assays, we observed that γ-H2AX, p53, acetyl-H3, p300 and c-Jun were consistently recruited by UV to a distinct region (−2067/−1768) adjacent to the p300 binding site (−1858/−1845) in the MMP-1 promoter. In addition, these recruitments of γ-H2AX, p53, acetyl-H3, p300 and c-Jun to the p300-2 site were significantly abrogated by post-treatment with AA. Furthermore, overexpression of p300 increased the basal and UV-induced MMP-1 promoter activity. Our results suggest that p300HAT plays a critical role in the transcriptional regulation of MMP-1 by UV

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2000). A novel transcriptional repression domain mediates p21(WAF1/CIP1) induction of p300 transactivation.
  2. (2006). Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1).
  3. (1996). Adenovirus E1A downregulates cJunand JunB-mediated transcription by targeting their coactivator p300.
  4. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
  5. (2000). CBP/ p300 histone acetyl-transferase activity is important for the G1/S transition.
  6. (1996). Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase13 from human osteoarthritic cartilage.
  7. (1999). Crystal structures of MMP-1 and 213 reveal the structural basis for selectivity of collagenase inhibitors.
  8. (1998). DNA damage activates p53 through a phosphorylation-acetylation cascade.
  9. (2005). E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation.
  10. (2003). Enhanced expression of cylooxygenase-2 by UV in aged human skin in vivo.
  11. (1999). Function for p300 and not CBP in the apoptotic response to DNA damage.
  12. (2004). Heat shock-induced matrix metalloproteinase (MMP)-1 and MMP-3 are mediated through ERK and JNK activation and via an autocrine interleukin-6 loop.
  13. (2005). Histone acetylation, chromatin remodelling and nucleotide excision repair: hint from the study on MFA2 in Saccharomyces cerevisiae.
  14. (1995). IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes.
  15. (1995). Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA.
  16. (2003). Induction of p53-dependent activation of the human proliferating cell nuclear antigen gene in chromatin by ionizing radiation.
  17. (2006). Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation.
  18. (1993). Matrix metalloproteinases: a review. Crit Rev Oral
  19. (2001). Mechanisms of photodamage of the skin and its functional consequences for skin ageing.
  20. (2004). Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53.
  21. (2007). p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint.
  22. (2003). p53 is a chromatin accessibility factor for nucleotide excision repair of DNA damage.
  23. (1999). p53-dependent apoptosis or growth arrest induced by different forms of radiation in U2OS cells: p21WAF1/CIP1 repression in UV induced apoptosis.
  24. (2006). Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo.
  25. (2006). Redoxdependent matrix metalloproteinase-1 expression is regulated by JNK through Ets and AP-1 promoter motifs.
  26. (1999). Role for p300 in stabilization of p53 in the response to DNA damage.
  27. (2005). Sancar A
  28. (2003). Small molecule modulators of histone acetyltransferase p300.
  29. (2006). Small-molecule inhibitors of histone acetyltransferase activity: identification and biological properties.
  30. (2000). Structural differences of matrix metalloproteinases. Homology modeling and energy minimization of enzymesubstrate complexes.
  31. (2003). The activation domains, the proline-rich domain, and the C-terminal basic domain in p53 are necessary for acetylation of histones on the proximal p21 promoter and interaction with p300/CREB-binding protein.
  32. (2006). The FATC domains of PIKK proteins are functionally equivalent and participate in the Tip60-dependent activation of DNA-PKcs and ATM.
  33. (2000). The language of covalent histone modifications.
  34. (2005). The transcriptional coactivator p300 plays a critical role in the hypertrophic and protective pathways induced by phenylephrine in cardiac cells but is specific to the hypertrophic effect of urocortin.
  35. (2005). Transcriptome analysis reveals cyclobutane pyrimidine dimers as a major source of UV-induced DNA breaks.
  36. (1999). Transforming growth factor-beta induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase.
  37. (2001). Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways.
  38. (2001). Ultraviolet radiation increases tropoelastin mRNA expression in the epidermis of human skin in vivo.
  39. (2002). Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events.
  40. (2003). Upregulation of the matrix metalloproteinase-1 gene by the Ewing’s sarcoma associated EWS-ER81 and EWS-Fli-1 oncoproteins, c-Jun and p300.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.