Simple histone acetylation plays a complex role in the regulation of gene expression

Abstract

Eukaryotic DNA is packaged into chromatin by histone proteins, which assemble the DNA into an organized, higher-order structure. The precise organization of chromatin is essential for faithful execution of DNA-mediated reactions such as transcription, DNA replication, DNA repair and DNA recombination. The organization of chromatin is considered to be regulated by a variety of post-translational modifications of histones, such as acetylation, methylation, phosphorylation, ubiquitination, SUMOylation and poly-ADP-ribosylation. The relationship between histone acetylation and gene expression was first observed in 1964. Since then, a great deal of evidence has accumulated showing that not only transcription but other DNA-mediated reactions also are regulated by histone acetylation. With regard to the putative mechanism(s) by which histone acetylation regulates the flow of genetic information, site-specific modification and recognition of acetylated histone/DNA complexes have been postulated. Elucidation of the downstream effects of histone modification, as well as the identification, isolation and characterization of the relevant factors involved, have aided in our understanding of the mechanisms of regulation of DNA activity by histones. Currently, state-of-the-art technologies that enable genome-wide analysis are allowing insight into a critical and interesting question in eukaryotic transcription: are the principles that govern transcription of individual gene loci applicable to the genome as a whole? Here, we review the recent progress on histone modifications, with an emphasis on the role of histone acetylation in gene expression.

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

“…Chromatin remodeling by histone modifications plays a key role in the regulation of cellular processes, including gene transcription/repression, DNA repair, differentiation, and proliferation. Post-translational histone modifications predominantly occur via acetylation/ deacetylation and methylation/demethylation reactions (41,127) (Fig. 1).…”

Suppression of lipopolysaccharide- and tumour necrosis factor-α-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation

“…Under resting conditions, DNA forms a 'closed chromatin structure' excluding the binding of RNA polymerase II (Pol II), transcription factors and other large protein complexes leading to gene silencing or repression [4,5]. In stimulated cells, transcription factors such as nuclear factor (NF)-kB, activator protein (AP)-1 and signal transducers and activators of transcription (STAT)s are activated and translocate to the nucleus, bind DNA and subsequently recruit co-activator molecules, such as CREB-binding protein (CBP), p300, GCN5 and PCAF [6,7].…”

Global analysis of histone lysine acetylation and proteomic changes in EC109 cells treated with the histone deacetylase inhibitor FK228

“…The electrospray voltage applied was 1.8 kV. Automatic gain control was used to prevent overfilling of the ion trap; 1x10 5 ions were accumulated for generation of the MS/MS spectra. For the MS scans, the m/z scan range was between 350 and 1,600 Da.…”

“…Histone acetylation status is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs), which are associated with chromatin structure and influence gene transcription (3)(4)(5). HATs direct the addition of acetyl groups to lysine residues on histones and regulate gene expression.…”