{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T15:55:47Z","timestamp":1720281347174},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T00:00:00Z","timestamp":1339718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The loss\u2010of\u2010function of ten\u2013eleven\u2010translocation (TET) 2, a Fe<jats:sup>2+<\/jats:sup>\u2010oxoglutarate\u2010dependent dioxygenase catalyzing 5 methyl cytosine (5mC) conversion into 5\u2010hydroxymethylcytosine (5hmC), contributes to the hematopoietic transformation in vivo. The aim of our study was to elucidate its role in the phenotype of chronic myeloid leukemia (CML), a myeloproliferative disease caused by the Bcr\u2010Abl rearranged gene. We first confirmed TET2 interaction with the Bcr\u2010Abl protein predicted by a Fourier\u2010based bioinformatic method. Such interaction led to TET2 cytoplasmatic compartmentalization in a complex tethered by the fusion protein tyrosine kinase (TK) and encompassing the Forkhead box O3a (FoxO3a) transcription factor. We then focused the impact of TET2 loss\u2010of\u2010function on epigenetic transcriptional regulation of Bcl2\u2010interacting mediator (BIM), a pro\u2010apoptotic protein transcriptionally regulated by FoxO3a. BIM downregulation is a critical component of CML progenitor extended survival and is also involved in the disease resistance to imatinib (IM). Here we reported that TET2 release from Bcr\u2010Abl protein following TK inhibition in response to IM triggers a chain of events including TET2 nuclear translocation, re\u2010activation of its enzymatic function at 5mC and recruitment at the BIM promoter followed by BIM transcriptional induction. 5hmC increment following TET2 re\u2010activation was associated with the reduction of histone H3 tri\u2010methylation at lysine 9 (H3K9me3), which may contribute with DNA de\u2010methylation reported elsewhere to recast a permissive epigenetic \u201clandscape\u201d for FoxO3a transcriptional activity. J. Cell. Biochem. 113: 2765\u20132774, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24154","type":"journal-article","created":{"date-parts":[[2012,4,3]],"date-time":"2012-04-03T13:36:33Z","timestamp":1333460193000},"page":"2765-2774","source":"Crossref","is-referenced-by-count":17,"title":["Cytoplasmatic compartmentalization by Bcr\u2010Abl promotes TET2 loss\u2010of\u2010function in chronic myeloid 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