Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-21
pubmed:abstractText
Activating 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 1? (HP1?). Levels of chromatin-bound HP1? 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 HP1? 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.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-10077599, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-10364425, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-10428964, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-11484059, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-11934592, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-12524553, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-12618378, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-12787505, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-14636556, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-14696356, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-15328362, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-1534254, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-15781101, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-15793561, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-15837627, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-15858187, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-16199153, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-16199517, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-16767105, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-16892059, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-17151367, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-17224923, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-17541402, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-17603471, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-17660197, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-17660198, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18184035, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18239084, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18344984, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18497825, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18536715, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18600261, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18779404, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-18837461, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-19020503, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-19571317, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-19571885, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-19783980, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-19884255, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-19884257, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-20489053, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-3143916, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-3143917, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-3143918, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-4827655, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-7888668, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-8377226, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-8608586, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-8939963, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-9590172, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-9590173, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-9590174, http://linkedlifedata.com/resource/pubmed/commentcorrection/21151131-9649508
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-4679
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13-21
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
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