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MMP28 gene expression is regulated by Sp1 transcription factor acetylation

Lookup NU author(s): Professor David YoungORCiD


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MMP-28 (epilysin) is a recently cloned member of the MMP (matrix metalloproteinase) family. It is highly expressed in the skin by keratinocytes, the developing and regenerating nervous system and a number of other normal human tissues, as well as a number of carcinomas. The MMP28 promoter has previously been cloned and characterized identifying a conserved GT-box that binds Sp1/Sp3 (specificity proteins I and 3) proteins and is essential for the basal expression of the gene. The present study demonstrates that MMP28 expression is induced by HDAC (histone deacetylase) inhibitors and that this effect is mediated through the GT-box. Transient transfection assays have shown that the induction of MMP28 expression by the HDAC inhibitior TSA (trichostatin A) is mediated via Sp1 at the GT-box. Immunoprecipitation experiments have shown that the acetylation of Sp1 and Sp3 is increased by TSA treatment; however, no effect on DNA binding was observed. Histone acetyltransferases such as p300 and P/CAF [p300/CREB (cAMP-response-element-binding protein)binding protein-associated factor] increased induction of the MMP28 promoter by Sp1. Knockdown of HDAC1 using siRNA (small interfering RNA) also induces the MMP28 promoter. Oligonucleotide pulldown identified STRAP (serine/threonine kinase receptor-associated protein) as a further protein recruited to the MMP28 promoter and acting functionally with Sp1.

Publication metadata

Author(s): Swingler TE, Kevorkian L, Culley KL, Illman SA, Young DA, Parker AE, Lohi J, Clark IM

Publication type: Article

Publication status: Published

Journal: Biochemical Journal

Year: 2010

Volume: 427

Pages: 391-400

Print publication date: 09/02/2010

Date deposited: 09/06/2010

ISSN (print): 0264-6021

ISSN (electronic): 1470-8728

Publisher: Portland Press Ltd.


DOI: 10.1042/BJ20091798


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Funder referenceFunder name
Dunhill Medical Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
073379/Z/03/ZWellcome Trust