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Volume 272, Number 9, Issue of February 28, 1997 pp. 5871-5879
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Role of Positive and Negative Cis-regulatory Elements in the Transcriptional Activation of the Lysozyme Locus in Developing Macrophages of Transgenic Mice

(Received for publication, October 9, 1996, and in revised form, November 22, 1996)

From the Institut für Biologie III der Universität Freiburg, Schänzlestrasse 1, D-79104 Freiburg and ^§ Max Planck Institut für Immunbiologie, Stübeweg 51, 79108 Freiburg, Federal Republic of Germany

Expression of the chicken lysozyme locus in macrophages is regulated by at least six different positive and negative cis-regulatory elements. Chromatin of the chicken lysozyme locus is gradually reorganized during macrophage differentiation, indicating that each cis-regulatory element is activated at a different developmental stage. Irrespective of their differential developmental activation, individual cis-regulatory regions are capable of driving transcription of the lysozyme gene in mature macrophages of transgenic mice. In order to examine the role of different cis-regulatory regions in lysozyme locus activation, we analyzed the time course of transcriptional up-regulation of deletion mutants of the lysozyme locus in a new in vitro differentiation system based on enriched primary macrophage precursor cells from the bone marrow of transgenic mice. We show that constructs carrying cis-regulatory elements which are structurally reorganized early in development are also transcriptionally active at an early stage. A construct in which the early enhancer has been deleted shows a delay in transcriptional activation. The presence or absence of a negative regulatory element has no influence on the time course of transcriptional activation of the lysozyme locus.

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