Potential role for PADI-mediated histone citrullination in preimplantation development.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2012-06-19Keywords
AnimalsBlastocyst
Citrulline
Embryonic Development
Female
Histones
Hydrolases
Hydroxamic Acids
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Oocytes
Ornithine
Biochemistry
Developmental Biology
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
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Show full item recordAbstract
BACKGROUND: The peptidylarginine deiminases (PADIs) convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated. RESULTS: In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26) were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA) to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17. CONCLUSIONS: Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is permissive for histone acetylation.Source
BMC Dev Biol. 2012 Jun 19;12:19. doi: 10.1186/1471-213X-12-19. Link to article on publisher's siteDOI
10.1186/1471-213X-12-19Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50025Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
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Link to Article in PubMedRights
© 2012 Kan et al.;licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.ae974a485f413a2113503eed53cd6c53
10.1186/1471-213X-12-19