Mi2 Shows Chromatin Enzyme Specificity by Erasing a DNase I-hypersensitive Site Established by ACF

Graduate Program in Biophysics and Structural Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 02/2009; 284(12):7533-41. DOI: 10.1074/jbc.M807617200
Source: PubMed


ATP-dependent chromatin-remodeling enzymes are linked to changes in gene expression; however, it is not clear how the multiple
remodeling enzymes found in eukaryotes differ in function and work together. In this report, we demonstrate that the ATP-dependent
remodeling enzymes ACF and Mi2β can direct consecutive, opposing chromatin-remodeling events, when recruited to chromatin
by different transcription factors. In a cell-free system based on the immunoglobulin heavy chain gene enhancer, we show that
TFE3 induces a DNase I-hypersensitive site in an ATP-dependent reaction that requires ACF following transcription factor binding
to chromatin. In a second step, PU.1 directs Mi2β to erase an established DNase I-hypersensitive site, in an ATP-dependent
reaction subsequent to PU.1 binding to chromatin, whereas ACF will not support erasure. Erasure occurred without displacing
the transcription factor that initiated the site. Other tested enzymes were unable to erase the DNase I-hypersensitive site.
Establishing and erasing the DNase I-hypersensitive site required transcriptional activation domains from TFE3 and PU.1, respectively.
Together, these results provide important new mechanistic insight into the combinatorial control of chromatin structure.

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    • "CD4 silencer), the simplest explanation is they are doing different things. Some examples where different remodeling enzymes are recruited to the same locus in cell-free (Ishii et al., 2009) and cell based systems (Gao et al., 2009; Precht et al., 2010; Ramirez-Carrozzi et al., 2006) illustrate this point. ATP-dependent remodeling has been found to alter histone modifications, a simple illustration of remodeling enzymes having different roles at the same locus (DiRenzo et al., 2000; Letimier et al., 2007; Ramirez-Carrozzi et al., 2006; Wurster and Pazin, 2008). "
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