Inducible covalent posttranslational modification of histone H3.
The physiological state of a eukaryotic cell is determined by endogenous and exogenous signals, and often the endpoint of the pathways that transmit these signals is DNA. DNA is organized into chromatin, a nucleoprotein complex, which not only facilitates the packaging of DNA within the nucleus but also serves as an important factor in the regulation of gene function. The nucleosome is the basic unit of chromatin and generally consists of approximately two turns of DNA wrapped around an octamer of core histone proteins. Each histone also contains an accessible N-terminal tail that extends outside the chromatin complex and is subject to posttranslational modifications that are crucial in the regulation of gene expression. Two distinct categories of histone posttranslational modification have been observed: (i) inducible or stimulation-dependent and (ii) mitosis-dependent. Stimulation by mitogens or stress leads to rapid transient posttranslational modifications of histones, in particular histone H3, which are mechanistically and temporarily distinct from modifications associated with mitosis. This Review focuses mainly on the inducible phosphorylation of histone H3 brought about by different stimuli, such as epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, arsenite, or ultraviolet radiation. We examine the most recent, and at times controversial, research data concerning the identity of the histone H3 kinases responsible for this phosphorylation. In addition, the interdependence of phosphorylation and acetylation will be discussed in light of data showing patterns of inducible modification at specific genes.
Bode
Ann M
AM
Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, USA. ambode@hi.umn.edu
Dong
Zigang
Z
D000107:Acetylation / Q000187:drug effects / Q000528:radiation effects; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000648:ultrastructure; D004789:Enzyme Activation; D004790:Enzyme Induction; D005057:Eukaryotic Cells / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008745:Methylation / Q000187:drug effects / Q000528:radiation effects; D008934:Mitogens / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry / Q000648:ultrastructure; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D006656:Protamine Kinase / Q000378:metabolism; D011487:Protein Conformation; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011496:Protein Methyltransferases; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D017434:Protein Structure, Tertiary; D013312:Stress, Physiological / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D002843:Chromatin; D006657:Histones; D008934:Mitogens; D009707:Nucleosomes; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D011494:Protein Kinases; D006656:Protamine Kinase