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dc.contributor.authorReyes-Gutierrez, Pablo
dc.contributor.authorCarrasquillo-Rodriguez, Jake W.
dc.contributor.authorImbalzano, Anthony N.
dc.date2022-08-11T08:09:54.000
dc.date.accessioned2022-08-23T16:47:56Z
dc.date.available2022-08-23T16:47:56Z
dc.date.issued2019-08-20
dc.date.submitted2019-09-19
dc.identifier.citation<p>PLoS One. 2019 Aug 20;14(8):e0216015. doi: 10.1371/journal.pone.0216015. eCollection 2019. <a href="https://doi.org/10.1371/journal.pone.0216015">Link to article on publisher's site</a></p>
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0216015
dc.identifier.pmid31430278
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41174
dc.description.abstractJMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids that mediate binding of iron and 2-oxogluterate, which are required cofactors for enzymatic activity, had no impact on JMJD6 function, showing that catalytic activity is not required for JMJD6 contributions to adipogenic differentiation. In addition, we documented the formation of JMJD6 oligomers and showed that catalytic activity is not required for oligomerization, as has been reported previously. We also observed no effect of mutations in the sumoylation site and in the poly-serine stretch. In contrast, mutation of the AT hook-like structure, which mediates interaction with DNA and/or RNA, compromised JMJD6 function by blocking its ability to interact with chromatin at genes that express regulators of adipogenesis. The ability of JMJD6 to interact with nucleic acids may be a critical requirement for its function in adipogenic differentiation. The requirement for the AT hook-like domain and the lack of requirement for catalytic activity giving rise to the idea that co-activation of transcription by JMJD6 may be functioning as a scaffold protein that supports the interactions of other critical regulators.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31430278&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright: © 2019 Reyes-Gutierrez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPoint mutation
dc.subjectCell differentiation
dc.subjectChromatin
dc.subjectGene expression
dc.subjectOils
dc.subjectTranscriptional control
dc.subjectProtein domains
dc.subjectSequence motif analysis
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectEnzymes and Coenzymes
dc.subjectMolecular Biology
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectStructural Biology
dc.titlePromotion of adipogenesis by JMJD6 requires the AT hook-like domain and is independent of its catalytic function
dc.typeJournal Article
dc.source.journaltitlePloS one
dc.source.volume14
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4978&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3962
dc.identifier.contextkey15377571
refterms.dateFOA2022-08-23T16:47:56Z
html.description.abstract<p>JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids that mediate binding of iron and 2-oxogluterate, which are required cofactors for enzymatic activity, had no impact on JMJD6 function, showing that catalytic activity is not required for JMJD6 contributions to adipogenic differentiation. In addition, we documented the formation of JMJD6 oligomers and showed that catalytic activity is not required for oligomerization, as has been reported previously. We also observed no effect of mutations in the sumoylation site and in the poly-serine stretch. In contrast, mutation of the AT hook-like structure, which mediates interaction with DNA and/or RNA, compromised JMJD6 function by blocking its ability to interact with chromatin at genes that express regulators of adipogenesis. The ability of JMJD6 to interact with nucleic acids may be a critical requirement for its function in adipogenic differentiation. The requirement for the AT hook-like domain and the lack of requirement for catalytic activity giving rise to the idea that co-activation of transcription by JMJD6 may be functioning as a scaffold protein that supports the interactions of other critical regulators.</p>
dc.identifier.submissionpathoapubs/3962
dc.contributor.departmentBiochemistry and Molecular Pharmacology
dc.source.pagese0216015


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Copyright: © 2019 Reyes-Gutierrez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2019 Reyes-Gutierrez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.