Participation of histones and histone-modifying enzymes in cell functions through alterations in chromatin structure

Alterations in the chromatin structure are preferentially involved in the r egulation of cell functions, including gene expression, in eukaryotes, Thre e types of mechanisms, by which the alterations are caused have been report ed: (i) variants of histone subtypes, (ii) chromatin remodeling, and (iii) post-translational modification. This review focuses mainly on the first an d third mechanisms, especially on the acetylation of core histones, one of the third mechanisms. Using the gene targeting technique for the DT40 chick en B cell line, we systematically generated a number of mutants, respective ly, devoid of particular genes encoding histones and histone deacetylase(s) (HDACs), Most of the ill and core histone variants should be involved posi tively or negatively in the transcription regulation of particular genes. O f the chicken HDACs (chHDACs), chHDAC-2 controls the amount of the IgM H-ch ain at the steps of both transcription and alternative pre-mRNA processing, and chHDAC-3 is essential for cell viability, whereas chHDAC-1 merely affe cts gene expression in DT40 cells. These results indicate that HDAC family members should participate, in combination with one another, and/or histone acetyltransferase(s) (HATs), in the acetylation of core histones that regu lates gene expression through alterations in the chromatin structure.