File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease

TitleLIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease
Authors
Issue Date2011
Citation
Nature Cell Biology, 2011, v. 13, n. 1, p. 13-21 How to Cite?
AbstractActivating mutations in the tyrosine kinase Janus kinase 2 (JAK2) cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. Leukaemia inhibitory factor (LIF) signalling through the JAK-signal transducer and activator of transcription (STAT) pathway enables self-renewal of embryonic stem (ES) cells. Here we show that mouse ES cells carrying the human JAK2V617F mutation were able to self-renew in chemically defined conditions without cytokines or small-molecule inhibitors, independently of JAK signalling through the STAT3 or phosphatidylinositol-3-OH kinase pathways. Phosphorylation of histone H3 tyrosine 41 (H3Y41) by JAK2 was recently shown to interfere with binding of heterochromatin protein 1α (HP1α). Levels of chromatin-bound HP1α were lower in JAK2V617F ES cells but increased following inhibition of JAK2, coincident with a global reduction in histone H3Y41 phosphorylation. JAK2 inhibition reduced levels of the pluripotency regulator Nanog, with a reduction in H3Y41 phosphorylation and concomitant increase in HP1Î ± levels at the Nanog promoter. Furthermore, Nanog was required for factor independence of JAK2V617F ES cells. Taken together, these results uncover a previously unrecognized role for direct signalling to chromatin by JAK2 as an important mediator of ES cell self-renewal. © 2011 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/249045
ISSN
2023 Impact Factor: 17.3
2023 SCImago Journal Rankings: 8.913
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGriffiths, Dean S.-
dc.contributor.authorLi, Juan-
dc.contributor.authorDawson, Mark A.-
dc.contributor.authorTrotter, Matthew W.B.-
dc.contributor.authorCheng, Yi Han-
dc.contributor.authorSmith, Aileen M.-
dc.contributor.authorMansfield, William-
dc.contributor.authorLiu, Pentao-
dc.contributor.authorKouzarides, Tony-
dc.contributor.authorNichols, Jennifer-
dc.contributor.authorBannister, Andrew J.-
dc.contributor.authorGreen, Anthony R.-
dc.contributor.authorGöttgens, Berthold-
dc.date.accessioned2017-10-27T05:58:57Z-
dc.date.available2017-10-27T05:58:57Z-
dc.date.issued2011-
dc.identifier.citationNature Cell Biology, 2011, v. 13, n. 1, p. 13-21-
dc.identifier.issn1465-7392-
dc.identifier.urihttp://hdl.handle.net/10722/249045-
dc.description.abstractActivating mutations in the tyrosine kinase Janus kinase 2 (JAK2) cause myeloproliferative neoplasms, clonal blood stem cell disorders with a propensity for leukaemic transformation. Leukaemia inhibitory factor (LIF) signalling through the JAK-signal transducer and activator of transcription (STAT) pathway enables self-renewal of embryonic stem (ES) cells. Here we show that mouse ES cells carrying the human JAK2V617F mutation were able to self-renew in chemically defined conditions without cytokines or small-molecule inhibitors, independently of JAK signalling through the STAT3 or phosphatidylinositol-3-OH kinase pathways. Phosphorylation of histone H3 tyrosine 41 (H3Y41) by JAK2 was recently shown to interfere with binding of heterochromatin protein 1α (HP1α). Levels of chromatin-bound HP1α were lower in JAK2V617F ES cells but increased following inhibition of JAK2, coincident with a global reduction in histone H3Y41 phosphorylation. JAK2 inhibition reduced levels of the pluripotency regulator Nanog, with a reduction in H3Y41 phosphorylation and concomitant increase in HP1Î ± levels at the Nanog promoter. Furthermore, Nanog was required for factor independence of JAK2V617F ES cells. Taken together, these results uncover a previously unrecognized role for direct signalling to chromatin by JAK2 as an important mediator of ES cell self-renewal. © 2011 Macmillan Publishers Limited. All rights reserved.-
dc.languageeng-
dc.relation.ispartofNature Cell Biology-
dc.titleLIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ncb2135-
dc.identifier.pmid21151131-
dc.identifier.scopuseid_2-s2.0-78650516974-
dc.identifier.volume13-
dc.identifier.issue1-
dc.identifier.spage13-
dc.identifier.epage21-
dc.identifier.isiWOS:000285502200006-
dc.identifier.issnl1465-7392-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats