Rendez-vous at mitosis: TRRAPed in the chromatin.
Cell cycle progression and cell cycle checkpoints are guided by dynamic changes in gene expression that requires concerted efforts of chromatin modifying/remodeling activities and transcription machinery. Epigenetic modifications including acetylation of specific lysine residues within the amino-terminal tails of core histones play an important role in these processes. In the last few years, a flurry of biochemical studies has identified numerous histone acetyltransferases (HAT) whose activity is dependent on the multiprotein assemblies and responsible for histone acetylation. In addition to their well-known involvement in the control of gene transcription, recent studies implicated HATs and histone acetylation in other important cellular processes, such as DNA replication, cell cycle control, DNA repair and genomic stability. With the exception of catalytic subunits of the HAT assemblies, the role of other components of these large multi-subunit complexes in cellular processes remains largely unknown. Recent genetic and cellular studies have shown that Trrap, a common component of HAT complexes, regulates the mitotic checkpoint function by modulation of mitotic checkpoint genes. This regulation involves a concerted and cell cycle stage-coupled recruitment of HAT activity to promoters of specific checkpoint genes, providing a functional link between specific chromatin modifications and cell cycle control. These findings shed new light on the role of HAT components and histone acetylation in cell cycle control and underscore functional significance of epigenetic modifications in cellular processes.
Herceg
Zdenko
Z
Group of Gene-Environment Biology, Genetics and Epidemiology Cluster, International Agency for Research on Cancer, Lyon, France. herceg@iarc.fr
Wang
Zhao-Qi
ZQ
D000123:Acetyltransferases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002453:Cell Cycle; D048750:Cell Nucleus Division; D002843:Chromatin / Q000737:chemistry / Q000502:physiology*; D002875:Chromosomes / Q000648:ultrastructure; D004249:DNA Damage; D004260:DNA Repair; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D016678:Genome; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology*; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C113829:transformation-transcription domain-associated protein; D000123:Acetyltransferases; D051548:Histone Acetyltransferases