The DNA-histone complex in eukaryotic nuclei is called chromatin. In chromatin, histones (H1, H2A, H2B, H3 and H4), which are low-molecular-weight proteins, tightly bind with DNA, because all the histones are positively charged and DNA is negatively charged. The electrostatic DNA-histone interactions are significantly involved in the formation of the chromatin structure. Alterations in the chromatin structure are essential for access of various transcription factors to chromosomal DNA in eukaryotic cells. Histone acetyltransferases (HATs) catalyze acetylation of core histones resulting in attenuation of the electrostatic DNA-histone interactions. In contrast, histone deacetylases (HDACs) remove acetyl groups from the acetylated histones resulting in recovery of the interactions. Control of histone acetylation/deacetylation levels by HATs and HDACs is a significant mechanism for transcriptional regulation through alterations in the chromatin structure. General control non-depressible 5 (GCN5) belonging to GCN5-family HATs, which consist of GCN5 and p300/CBP-associated factor (PCAF), was first identified as a global coactivator and transcription-related HAT. GCN5 mainly catalyzes acetylation of histones H2B, H3 and H4 that is an important modification for epigenetic transcriptional activation. The importance of GCN5 is also emphasized by some studies revealing that GCN5-knockout mice die during embryogenesis. In this review article concerning our own past studies, we describe various inherent physiological functions of GCN5, which were revealed by us using gene targeting techniques in chicken immature B cell line DT40 cells: (i) regulation of cell cycle and cell proliferation, (ii) regulation of B cell receptor-mediated apoptosis related to negative selection of B cells, (iii) regulation of superoxide generation in leukocytes, (iv) regulation of response to hydrogen peroxide-induced oxidative stress, (v) regulation of UV-tolerance, (vi) regulation of B cell differentiation, and (vii) regulation of endoplasmic reticulum stress-induced apoptosis. Thus, we show that gene targeting techniques in DT40 cells can be a powerful tool for the functional analysis of GCN5. Our results, together with enormous previous data, significantly contribute to the elucidation of inherent physiological functions of GCN5.
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