Combinatorial Control of DNase I-hypersensitive Site Formation and Erasure by Immunoglobulin Heavy Chain Enhancer-binding Proteins

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Abstract

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.

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Ishii, H., Sen, R., & Pazin, M. J. (2004). Combinatorial Control of DNase I-hypersensitive Site Formation and Erasure by Immunoglobulin Heavy Chain Enhancer-binding Proteins. Journal of Biological Chemistry, 279(8), 7331–7338. https://doi.org/10.1074/jbc.M308973200

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