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J. Biol. Chem., Vol. 283, Issue 50, 35140-35153, December 12, 2008

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Yin Yang 1 Is a Critical Repressor of Matrix Metalloproteinase-9 Expression in Brain Neurons^*

Marcin Rylski¹, Renata Amborska, Katarzyna Zybura, Barbara Mioduszewska, Piotr Michaluk, Jacek Jaworski^¶, and Leszek Kaczmarek²

From the Department of Molecular and Cellular Neurobiology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland, the Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands, and the ^¶Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland

Membrane depolarization controls long lasting adaptive neuronal changes in brain physiology and pathology. Such responses are believed to be gene expression-dependent. Notably, however, only a couple of gene repressors active in nondepolarized neurons have been described. In this study, we show that in the unstimulated rat hippocampus in vivo, as well as in the nondepolarized brain neurons in primary culture, the transcriptional regulator Yin Yang 1 (YY1) is bound to the proximal Mmp-9 promoter and strongly represses Mmp-9 transcription. Furthermore, we demonstrate that monoubiquitinated and CtBP1 (C-terminal binding protein 1)-bound YY1 regulates Mmp-9 mRNA synthesis in rat brain neurons controlling its transcription apparently via HDAC3-dependent histone deacetylation. In conclusion, our data suggest that YY1 exerts, via epigenetic mechanisms, a control over neuronal expression of MMP-9. Because MMP-9 has recently been shown to play a pivotal role in physiological and pathological neuronal plasticity, YY1 may be implicated in these phenomena as well.

Received for publication, June 13, 2008 , and in revised form, October 15, 2008.

^* This work was supported by the Polish Ministry of Science and Higher Education Grant 2 P04A 081 29 and 7 FP European Union Grant MemStick. 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 To whom correspondence may be addressed. Tel.: 4822-659-3001; Fax: 4822-822-5342; E-mail: m.rylski{at}gmail.com.

² To whom correspondence may be addressed. Tel.: 4822-659-3001; Fax: 4822-822-5342; E-mail: l.kaczmarek{at}nencki.gov.pl.

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