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dc.contributor.authorKan, Rui
dc.contributor.authorJin, Mei
dc.contributor.authorSubramanian, Venkataraman
dc.contributor.authorCausey, Corey P.
dc.contributor.authorThompson, Paul R
dc.contributor.authorCoonrod, Scott A.
dc.date2022-08-11T08:11:00.000
dc.date.accessioned2022-08-23T17:28:11Z
dc.date.available2022-08-23T17:28:11Z
dc.date.issued2012-06-19
dc.date.submitted2015-05-22
dc.identifier.citationBMC Dev Biol. 2012 Jun 19;12:19. doi: 10.1186/1471-213X-12-19. <a href="http://dx.doi.org/10.1186/1471-213X-12-19">Link to article on publisher's site</a>
dc.identifier.issn1471-213X (Linking)
dc.identifier.doi10.1186/1471-213X-12-19
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50025
dc.description<p>At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.</p>
dc.description.abstractBACKGROUND: 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22712504&dopt=Abstract">Link to Article in PubMed</a>
dc.rights© 2012 Kan et al.;licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</a>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subjectAnimals
dc.subjectBlastocyst
dc.subjectCitrulline
dc.subjectEmbryonic Development
dc.subjectFemale
dc.subjectHistones
dc.subjectHydrolases
dc.subjectHydroxamic Acids
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Inbred Strains
dc.subjectOocytes
dc.subjectOrnithine
dc.subjectBiochemistry
dc.subjectDevelopmental Biology
dc.subjectEnzymes and Coenzymes
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectTherapeutics
dc.titlePotential role for PADI-mediated histone citrullination in preimplantation development.
dc.typeJournal Article
dc.source.journaltitleBMC developmental biology
dc.source.volume12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1034&amp;context=thompson&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/thompson/35
dc.identifier.contextkey7135700
refterms.dateFOA2022-08-23T17:28:11Z
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p>
dc.identifier.submissionpaththompson/35
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages19


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