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J. Biol. Chem., Vol. 279, Issue 29, 30689-30696, July 16, 2004

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Genome-wide Mapping of in Vivo Targets of the Drosophila Transcription Factor Krüppel^*

Alexey Matyash, Ho-Ryun Chung, and Herbert Jäckle

From the Max-Planck-Institut für biophysikalische Chemie, Abteilung Molekulare Entwicklungsbiologie, D-37070 Göttingen, Germany

Krüppel (Kr), a member of the gap class of Drosophila segmentation genes, encodes a DNA binding zinc finger-type transcription factor. In addition to its segmentation function at the blastoderm stage, Krüppel also plays a critical role in organ formation during later stages of embryogenesis. To systematically identify in vivo target genes of Krüppel, we isolated DNA fragments from the Krüppel-associated portion of chromatin and used them to find and map Krüppel-dependent cis-acting regulatory sites in the Drosophila genome. We show that Krüppel binding sites are not enriched in Krüppel-associated chromatin and that the clustering of Krüppel binding sites, as found in the cis-acting elements of Krüppel-dependent segmentation genes used for in silico searches of Krüppel target genes, is not a prerequisite for the in vivo binding of Krüppel to its regulatory elements. Results obtained with the newly identified target gene ken and barbie (ken) indicate that Krüppel represses transcription and thereby restricts the spatial expression pattern of ken during blastoderm and gastrulation.

Received for publication, March 25, 2004 , and in revised form, May 5, 2004.

^* This work was supported by the Max Planck Society. 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.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Fig. 1 and Tables 1 and 2.

A predoctoral fellow of the Boehringer Ingelheim Fonds.

To whom correspondence should be addressed. Tel.: 49-551-201-1482/3; Fax: 49-551-201-1755; E-mail: hjaeckl{at}gwdg.de.

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