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

J. Biol. Chem., Vol. 281, Issue 19, 13126-13133, May 12, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/19/13126    most recent M601194200v1 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 Gopalan, S. M. Articles by Kordula, T. Search for Related Content PubMed PubMed Citation Articles by Gopalan, S. M. Articles by Kordula, T. Social Bookmarking                      What's this?

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the ₁-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes^*

From the Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298

Discrete tissue-specific changes in chromatin structure of the distal serpin subcluster on human chromosome 14q32.1 allow a single gene encoding ₁-antichymotrypsin (ACT) to be expressed in astrocytes and glioma cells. This astrocyte-specific regulation involves activatory protein-1 (AP-1) because overexpression of dominant-negative c-jun(TAM67) abolishes ACT expression in glioma cells. Here we identify a new regulatory element, located within the –13-kb enhancer of the ACT gene, that binds nuclear factor-1 (NFI) and is indispensable for the full basal transcriptional activity of the ACT gene. Furthermore, down-regulation of NFI expression by siRNA abolishes basal ACT expression in glioma cells. However, NFI does not mediate astrocyte-specific expression by itself, but likely cooperates with AP-1. A detailed analysis of the 14-kb long 5'-flanking region of the ACT gene indicated the presence of adjacent NFI and AP-1 elements that colocalized with DNase I-hypersensitive sites found in astrocytes and glioma cells. Interestingly, knock-down of NFI expression also specifically abrogates the expression of glial acidic fibrillary protein (GFAP), which is an astrocyte-specific marker protein. Mutations introduced into putative NFI and AP-1 elements within the 5'-flanking region of the GFAP gene also diminished basal expression of the reporter. In addition, we found, using isoform-specific siRNAs, that NFI-X regulates the astrocyte-specific expression of ACT and GFAP. We propose that NFI-X cooperates with AP-1 by an unknown mechanism in astrocytes, which results in the expression of a subset of astrocyte-specific genes.

Received for publication, February 7, 2006 , and in revised form, March 22, 2006.

^* This work was supported by Grant NS044118 from the National Institutes of Health (to T. K.). 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 should be addressed. Tel.: 804-828-0771; Fax: 804-828-1473; E-mail: tkordula{at}vcu.edu.

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

This article has been cited by other articles:

				K. M. Wilczynska, S. K. Singh, B. Adams, L. Bryan, R. R. Rao, K. Valerie, S. Wright, I. Griswold-Prenner, and T. Kordula Nuclear Factor I Isoforms Regulate Gene Expression During the Differentiation of Human Neural Progenitors to Astrocytes Stem Cells, May 1, 2009; 27(5): 1173 - 1181. [Abstract] [Full Text] [PDF]

				B. S. Paugh, L. Bryan, S. W. Paugh, K. M. Wilczynska, S. M. Alvarez, S. K. Singh, D. Kapitonov, H. Rokita, S. Wright, I. Griswold-Prenner, et al. Interleukin-1 Regulates the Expression of Sphingosine Kinase 1 in Glioblastoma Cells J. Biol. Chem., February 6, 2009; 284(6): 3408 - 3417. [Abstract] [Full Text] [PDF]

				M.-E. Gingras, B. Masson-Gadais, K. Zaniolo, S. Leclerc, R. Drouin, L. Germain, and S. L. Guerin Differential Binding of the Transcription Factors Sp1, AP-1, and NFI to the Promoter of the Human {alpha}5 Integrin Gene Dictates Its Transcriptional Activity Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 57 - 67. [Abstract] [Full Text] [PDF]

				G. Barry, M. Piper, C. Lindwall, R. Moldrich, S. Mason, E. Little, A. Sarkar, S. Tole, R. M. Gronostajski, and L. J. Richards Specific Glial Populations Regulate Hippocampal Morphogenesis J. Neurosci., November 19, 2008; 28(47): 12328 - 12340. [Abstract] [Full Text] [PDF]

				D. Ai, J. Wang, M. Amen, M.-F. Lu, B. A. Amendt, and J. F. Martin Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development Mol. Cell. Biol., August 15, 2007; 27(16): 5765 - 5775. [Abstract] [Full Text] [PDF]

				K. Driller, A. Pagenstecher, M. Uhl, H. Omran, A. Berlis, A. Grunder, and A. E. Sippel Nuclear Factor I X Deficiency Causes Brain Malformation and Severe Skeletal Defects Mol. Cell. Biol., May 15, 2007; 27(10): 3855 - 3867. [Abstract] [Full Text] [PDF]