Independent Dynamic Regulation of Histone Phosphorylation and Acetylation during Immediate-Early Gene Induction

Abstract

Induction of c-fos and c-jun is associated with phosphoacetylation of histone H3 and acetylation of histone H4. Upon induction, a large population of nucleosomes becomes highly acetylated on histones H3 and H4, whereas a much smaller population of comparable nucleosomes at similar positions along the gene becomes phosphoacetylated. Inhibiting histone H3 phosphorylation with kinase inhibitors does not measurably alter the enhanced acetylation of these nucleosomes. Finally, whereas H3 phosphorylation is a MAP kinase-mediated inducible event, we found acetylation to be continuously turning over by the targeted action of HATs and HDACs in the absence of any stimulation or gene transcription. These studies suggest that phosphorylation and acetylation are independently and dynamically regulated at these genes and reveal the complexity of multiple histone modifications at immediate-early gene chromatin.

The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model

“…This decrease in acetylated H3 might be linked to nucleosomes loss instead of H3 deacetylation (Deckert and Struhl, 2001), but this seems rather unlikely as this loss would result in concomitant decrease in acetylated H4 level. H4 by TSA has already been described at the level of mouse mammary tumour virus and c-jun promoters (Thompson et al, 2001;Mulholland et al, 2003), and even ABCB1 promoter in CEMBcl2 cells (Baker et al, 2005). Nevertheless, it should be noted that the H3 acetylation level observed after 24 h TSA in H69VP cells was always above the basal value measured in untreated cells.…”

Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity

“…They showed enhanced histone H3 and H4 acetylation on c-jun nucleosome that was not phosphorylated. 31 This suggests that crosstalk between phosphorylation and acetylation of histones may depend on the precise manner in which a particular gene is connected up to the signaling pathway.…”

Epigenetic changes in virus-associated human cancers

“…On the other hand, histone proteins form octomers around DNA loops to form nucleosome, the individual packaging unit of genomic DNA. The histone tails that extrude from the nucleosomes can be modified by methylation [5], acetylation [6], phosphorylation [7], or ubiquitination [8] to creat potential combinations that have been referred as histone codes [9] in which gene regulatory information is concealed. Most recently, histone demethylase has been identified [10].…”