Abstract
Background:
Histone H3 clipping has been reported in chicken liver tissues and not in brain.
Results:
Glutamate dehydrogenase (GDH) is a histone H3-specific protease that clips free and chromatin-bound histone H3.
Conclusion:
GDH has the potential to act as a chromatin modifier and thereby regulates chromatin metabolism.
Significance:
GDH has been for the first time implicated in an epigenetic process.
Clipping of histone tails has been reported in several organisms. However, the significance and regulation of histone tail clipping largely remains unclear. According to recent discoveries H3 clipping has been found to be involved in regulation of gene expression and chromatin dynamics. Earlier we had provided evidence of tissue-specific proteolytic processing of histone H3 in White Leghorn chicken liver nuclei. In this study we identify a novel activity of glutamate dehydrogenase (GDH) as a histone H3-specific protease in chicken liver tissue. This protease activity is regulated by divalent ions and thiol-disulfide conversion
in vitro
. GDH specifically clips H3 in its free as well as chromatin-bound form. Furthermore, we have found an inhibitor that inhibits the H3-clipping activity of GDH. Like previously reported proteases, GDH too may have the potential to regulate/modulate post-translational modifications of histone H3 by removing the N-terminal residues of the histone. In short, our findings identify an unexpected proteolytic activity of GDH specific to histone H3 that is regulated by redox state, ionic concentrations, and a cellular inhibitor
in vitro
.