Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns.
Post-translational modifications of histones are determining factors in the global and local regulation of genome activity. Phosphorylation of histone H3 is globally associated with mitotic chromatin compaction but occurs in a much more restricted manner during interphase transcriptional regulation of a limited subset of genes. In the course of gene regulation, serine 10 phosphorylation at histone H3 is targeted to a very small fraction of nucleosomes that is highly susceptible to additional acetylation events. Recently, we and others have identified 14-3-3 as a binding protein that recognizes both phosphorylated serine 10 and phosphorylated serine 28 on histone H3. In vitro, the affinity of 14-3-3 for phosphoserine 10 is weak but becomes significantly increased by additional acetylation of either lysine 9 or lysine 14 on the same histone tail. In contrast, the histone H3S28 site matches elements of 14-3-3 high affinity consensus motifs. This region mediates an initial stronger interaction that is less susceptible to modulation by "auxiliary" modifications. Here we discuss the binding of 14-3-3 proteins to histone H3 in detail and putative biological implications of these interactions.
Winter
Stefan
S
Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Vienna, Austria.
Fischle
Wolfgang
W
Seiser
Christian
C
D048948:14-3-3 Proteins / Q000378:metabolism*; D000107:Acetylation; D000595:Amino Acid Sequence; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*
D048948:14-3-3 Proteins; D006657:Histones