Cynthia Wolberger, Professor, Department of Biophysics and Biophysical Chemistry at Johns Hopkins University School of Medicine, will give a talk on "Histone H2B ubiquitination in transcription and nucleosome dynamics"

ABSTRACT

Post-translational modifications of histones play a central role in regulating all cellular processes requiring access to DNA. Cross-talk between histone modifications, in which one histone modification regulates deposition of a second, provides an additional layer of regulation and specificity. Monoubiquitinated histone H2B-K120 (in humans; K123 in yeast) is a hallmark of actively transcribed genes that is required for methylation of histone H3K79 and H3K4, two other marks of active regions of transcription. H3K79 is methylated by Dot1L in humans and H3K4 is methylated by the COMPASS complex in yeast. To determine the molecular basis of cross-talk between histone ubiquitination and methylation, we have determined cryo-EM structures of the respective enzyme complexes bound to H2B-ubiquitinated nucleosomes. In addition to revealing the mechanism of ubiquitin recognition and enzyme stimulation, our studies have revealed surprising plasticity in the histone core of the nucleosome that has implications for interactions with other histone-modifying enzymes.