Scheme of Zbtb7a function at gene-regulatory elements.

<p>Cartoon outlining role of Zbtb7a described in this paper. Principal experimental evidence for each depicted step is shown in the indicated figures. (A) Top row: Zbtb7a binds to many genomic regulatory sites, including promoters and enhancers (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g002" target="_blank">Fig 2C and 2D</a>). Zbtb7a binding is independent of the presence of client TFs, and binding may occur before client TF recruitment (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">Fig 6A</a>). Second row: Zbtb7a-utilising client TFs bind independently to neighbouring genomic sites. This may occur under normal, steady-state conditions or in response to stimulation (see Figs <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g004" target="_blank">4A</a> and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6B</a>). Third row: Zbtb7a transduces TF-dependent changes in local chromatin accessibility (see Figs <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g004" target="_blank">4C</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g005" target="_blank">5D</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6C</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6D</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6E and 6F</a>). In the case of p65, this is triggered by the interaction between Zbtb7a and the TA3 region of p65 (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g005" target="_blank">Fig 5F</a>). Bottom row: Zbtb7a-transduced accessibility allows binding of secondary TFs and contributes to normal gene activation (see Figs <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g004" target="_blank">4D</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6G</a> and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.s005" target="_blank">S3L and S3M Fig</a>). (B) At genomic sites that lack Zbtb7a binding (which could occur due to the natural genomic distribution of Zbtb7 or through experimental manipulation), client TF binding is unimpaired (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">Fig 6B</a>), but Zbtb7a-dependent regulation of accessibility is abolished (see Figs <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g004" target="_blank">4C</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6C</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6D</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2004526#pbio.2004526.g006" target="_blank">6E and 6F</a>). TF, transcription factor.