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dc.contributor.authorGhule, Prachi N.
dc.contributor.authorBecker, Klaus A.
dc.contributor.authorHarper, J. Wade
dc.contributor.authorLian, Jane B.
dc.contributor.authorStein, Janet L.
dc.contributor.authorVan Wijnen, Andre J.
dc.contributor.authorStein, Gary S.
dc.date2022-08-11T08:08:57.000
dc.date.accessioned2022-08-23T16:13:53Z
dc.date.available2022-08-23T16:13:53Z
dc.date.issued2007-05-24
dc.date.submitted2008-09-11
dc.identifier.citationJ Cell Physiol. 2007 Oct;213(1):9-17. <a href="http://dx.doi.org/10.1002/jcp.21119">Link to article on publisher's site</a>
dc.identifier.issn0021-9541 (Print)
dc.identifier.doi10.1002/jcp.21119
dc.identifier.pmid17520687
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33732
dc.description.abstractHuman embryonic stem (ES) cells have an expedited cell cycle ( approximately 15 h) due to an abbreviated G1 phase ( approximately 2.5 h) relative to somatic cells. One principal regulatory event during cell cycle progression is the G1/S phase induction of histone biosynthesis to package newly replicated DNA. In somatic cells, histone H4 gene expression is controlled by CDK2 phosphorylation of p220(NPAT) and localization of HiNF-P/p220(NPAT) complexes with histone genes at Cajal body related subnuclear foci. Here we show that this 'S point' pathway is operative in situ in human ES cells (H9 cells; NIH-designated WA09). Immunofluorescence microscopy shows an increase in p220(NPAT) foci in G1 reflecting the assembly of histone gene regulatory complexes in situ. In contrast to somatic cells where duplication of p220(NPAT) foci is evident in S phase, the increase in the number of p220(NPAT) foci in ES cells appears to precede the onset of DNA synthesis as measured by BrdU incorporation. Phosphorylation of p220(NPAT) at CDK dependent epitopes is most pronounced in S phase when cells exhibit elevated levels of cyclins E and A. Our data indicate that subnuclear organization of the HiNF-P/p220(NPAT) pathway is rapidly established as ES cells emerge from mitosis and that p220(NPAT) is subsequently phosphorylated in situ. Our findings establish that the HiNF-P/p220(NPAT) gene regulatory pathway operates in a cell cycle dependent microenvironment that supports expression of DNA replication-linked histone genes and chromatin assembly to accommodate human stem cell self-renewal.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17520687&dopt=Abstract ">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/jcp.21119
dc.subjectCell Cycle; Cell Cycle Proteins; Cell Line; Coiled Bodies; Cyclins; Diatrizoate; Embryonic Stem Cells; Ficoll; Gene Expression Regulation; Humans; Nuclear Proteins; Phosphorylation
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleCell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220(NPAT) in human embryonic stem cells
dc.typeJournal Article
dc.source.journaltitleJournal of cellular physiology
dc.source.volume213
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/395
dc.identifier.contextkey627232
html.description.abstract<p>Human embryonic stem (ES) cells have an expedited cell cycle ( approximately 15 h) due to an abbreviated G1 phase ( approximately 2.5 h) relative to somatic cells. One principal regulatory event during cell cycle progression is the G1/S phase induction of histone biosynthesis to package newly replicated DNA. In somatic cells, histone H4 gene expression is controlled by CDK2 phosphorylation of p220(NPAT) and localization of HiNF-P/p220(NPAT) complexes with histone genes at Cajal body related subnuclear foci. Here we show that this 'S point' pathway is operative in situ in human ES cells (H9 cells; NIH-designated WA09). Immunofluorescence microscopy shows an increase in p220(NPAT) foci in G1 reflecting the assembly of histone gene regulatory complexes in situ. In contrast to somatic cells where duplication of p220(NPAT) foci is evident in S phase, the increase in the number of p220(NPAT) foci in ES cells appears to precede the onset of DNA synthesis as measured by BrdU incorporation. Phosphorylation of p220(NPAT) at CDK dependent epitopes is most pronounced in S phase when cells exhibit elevated levels of cyclins E and A. Our data indicate that subnuclear organization of the HiNF-P/p220(NPAT) pathway is rapidly established as ES cells emerge from mitosis and that p220(NPAT) is subsequently phosphorylated in situ. Our findings establish that the HiNF-P/p220(NPAT) gene regulatory pathway operates in a cell cycle dependent microenvironment that supports expression of DNA replication-linked histone genes and chromatin assembly to accommodate human stem cell self-renewal.</p>
dc.identifier.submissionpathgsbs_sp/395
dc.contributor.departmentDepartment of Cell Biology and Cancer Center
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages9-17


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