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Molecular and Cellular Biology, January 2001, p. 196-208, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.196-208.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Matrix Attachment Region-Dependent Function of the Immunoglobulin µ Enhancer Involves Histone Acetylation at a Distance without Changes in Enhancer Occupancy

Luis A. Fernández, Michael Winkler, and Rudolf Grosschedl*

Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143

Received 17 August 2000/Accepted 10 October 2000

Nuclear matrix attachment regions (MARs), which flank the immunoglobulin µ heavy-chain enhancer on either side, are required for the activation of the distal variable-region (VH) promoter in transgenic mice. Previously, we have shown that the MARs extend a local domain of chromatin accessibility at the µ enhancer to more distal sites. In this report, we examine the influence of MARs on the formation of a nucleoprotein complex at the enhancer and on the acetylation of histones, which have both been implicated in contributing to chromatin accessibility. By in vivo footprint analysis of transgenic µ gene constructs, we show that the occupancy of factor-binding sites at the µ enhancer is similar in transcriptionally active wild-type and transcriptionally inactive Delta MAR genes. Chromatin immunoprecipitation experiments indicate, however, that the acetylation of histones at enhancer-distal nucleosomes is enhanced 10-fold in the presence of MARs, whereas the levels of histone acetylation at enhancer-proximal nucleosomes are similar for wild-type and Delta MAR genes. Taken together, these data indicate that the function of MARs in mediating long-range chromatin accessibility and transcriptional activation of the VH promoter involves the generation of an extended domain of histone acetylation, independent of changes in the occupancy of the µ enhancer.

* Corresponding author. Present address: Gene Center and Institute of Biochemistry, Feodor Lynen Str. 25, 81377 Munich, Germany. Phone: (49-89) 2180-6901. Fax: (49-89) 2180-6949. E-mail: rgross{at}lmb.uni-muenchen.de.

Molecular and Cellular Biology, January 2001, p. 196-208, Vol. 21, No. 1
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.1.196-208.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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