Participation of histones, histone modifying enzymes and histone chaperones in vertebrate cell functions.

Abstract

Alterations in the chromatin structure are essential for easy accesses to chromosomal DNA. Such architectural alterations can be achieved by four means: (i) variants of histone subtypes, (ii) chromatin remodeling, (iii) post-translational modification, and (iv) chromatin assembly. This chapter discusses mainly on the first, third and fourth mechanisms, and especially on the acetylation of core histones, one of the third mechanisms. Taking the advantage of the gene targeting technique, we systematically established numerous mutant DT40 cell lines, each lacking particular gene, of interest such that encoding histones, histone deacetylases (HDACs), acetyltransferases (HATs) and chaperones, etc. Every subtype member of the histone gene family is capable of compensating the loss of others to maintain the mRNA level of each histone subtype, and most of histone variants are involved positively or negatively in the transcription regulation of particular genes. Regarding HDACs, HDAC-2 controls the amount of the IgM H-chain at the steps of both transcription and alternative pre-mRNA processing, and HDAC-3 is indispensable for cell viability. Concerning HATs, GCN5 has tremendous impact on growth kinetics by preferentially acting as a supervisor in the normal cell cycle progression. The distinct participatory roles of the N-terminal and C-terminal halves of HIRA, one of histone chaperones, in both cell growth and transcription regulations of cell cycle-related genes, have also been highlighted. Therefore, the gene targeting technique in the DT40 cell line can be used as a powerful tool for the functional analysis of histones, histone modifying enzymes and histone chaperones relevant to chromatin biology.