title: H3 clipping activity of glutamate dehydrogenase is regulated by stefin B and chromatin structure.
abstract: Glutamate dehydrogenase has been recently identified as a tissue-specific histone H3-specific clipping enzyme. We have previously shown that it cleaves free as well as chromatin-bound histone H3. However, the physiological significance of this enzyme is still not clear. The present study aimed to improve our understanding of its significance in vivo. Using biochemical and cell biological approaches, we show that glutamate dehydrogenase is primarily associated with euchromatin, and it re-localizes from the nuclear periphery to the nucleolus upon DNA damage. The cysteine protease inhibitor stefin B regulates the H3 clipping activity of the enzyme. Chromatin structure and certain histone modifications influence H3 clipping activity. Interestingly, we also observed that an in vivo truncated form of H3 lacks H3K56 acetylation, which is a code for the DNA damage response. Together, these results suggest that glutamate dehydrogenase is a euchromatin-associated enzyme, and its H3 clipping activity is regulated by chromatin structure, histone modifications and an in vivo inhibitor. In response to DNA damage, it re-localizes to the nuclei, and hence may be involved in regulation of gene expression in vivo.
authors.affiliation: Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
authors.forename: Papita
authors.initials: P
authors.lastname: Mandal
authors.forename: Sakshi
authors.initials: S
authors.lastname: Chauhan
authors.forename: Raghuvir S
authors.initials: RS
authors.lastname: Tomar
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D002645:Chickens; D002843:Chromatin / Q000737:chemistry*; D055313:Cystatin B / Q000502:physiology*; D004249:DNA Damage; D005786:Gene Expression Regulation; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational
chemical_list: C524994:CSTB protein, human; D002843:Chromatin; D006657:Histones; D055313:Cystatin B; D005969:Glutamate Dehydrogenase
keywords: H3 tail processing; chromatin structure; glutamate dehydrogenase; histone modification; stefin B