Jumonji histone demethylases catalyze removal of methyl marks from lysine residues in histone proteins within nucleosomes. Here, we show that the catalytic domain of demethylase JMJD2A (cJMJD2A) utilizes a distributive mechanism to remove the histone H3 lysine 9 trimethyl mark. By developing a method to assess demethylation of homogeneous, site-specifically methylated nucleosomes, we determined that the kinetic parameters for demethylation of nucleosomes by cJMJD2A are comparable to those of peptide substrates. These findings imply that other domains of the demethylase or its protein partners may contribute to nucleosome recognition in vivo and, in this way, may further regulate demethylation activity and processivity. The quantitative assays of nucleosome demethylation developed in our work provide a platform for future work with complex chromatin substrates and full-length demethylases.
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| http://dx.doi.org/10.1016/j.chembiol.2013.03.008 | DOI Listing |
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Article Synopsis
- PHF21A is a histone-binding protein that works with LSD1 and both proteins are important for neuron-specific splicing, impacting their functions in the brain.
- The study shows that during brain development, PHF21A expression happens before LSD1 expression, leading to reduced activity of their complex and altered methylation processes.
- PHF21A's unique microexon plays a crucial role in preventing excessive synapse formation by moderating LSD1's function, indicating its importance in proper neuronal development.
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