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J. Biol. Chem., Vol. 279, Issue 8, 7331-7338, February 20, 2004
Combinatorial Control of DNase I-hypersensitive Site Formation and Erasure by Immunoglobulin Heavy Chain Enhancer-binding Proteins*![]() ![]()
From the
DNase I-hypersensitive sites in cellular chromatin are usually believed to be nucleosome-free regions generated by transcription factor binding. Using a cell-free system we show that hypersensitivity does not simply correlate with the number of DNA-bound proteins. Specifically, the leucine zipper containing basic helix-loop-helix protein TFE3 was sufficient to induce a DNase I-hypersensitive site at the immunoglobulin heavy chain µ enhancer in vitro. TFE3 enhanced binding of an ETS protein PU.1 to the enhancer. However, PU.1 binding erased the DNase I-hypersensitive site without abolishing TFE3 binding. Furthermore, TFE3 binding enhanced transcription in the presence and absence of a hypersensitive site, whereas endonuclease accessibility correlated strictly with DNase I hypersensitivity. We infer that chromatin constraints for transcription and nuclease sensitivity can differ.
Received for publication, August 13, 2003 , and in revised form, November 21, 2003. * This work was supported the Cutaneous Biology Research Center, through the MGH/Shiseido Company agreement and the National Institutes of Health Grants GM61011 (to M. J. P.) and GM38925 (to R. S.). 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. || To whom correspondence should be addressed. Tel.: 617-726-5654; Fax: 617-726-4453; E-mail: michael.pazin{at}cbrc2.mgh.harvard.edu.
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