The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes
dc.contributor.author | Bakshi, Rachit | |
dc.contributor.author | Zaidi, Sayyed K. | |
dc.contributor.author | Pande, Sandhya | |
dc.contributor.author | Hassan, Mohammad Q. | |
dc.contributor.author | Young, Daniel W. | |
dc.contributor.author | Montecino, Martin A. | |
dc.contributor.author | Lian, Jane B. | |
dc.contributor.author | Van Wijnen, Andre J. | |
dc.contributor.author | Stein, Janet L. | |
dc.contributor.author | Stein, Gary S. | |
dc.date | 2022-08-11T08:08:04.000 | |
dc.date.accessioned | 2022-08-23T15:41:11Z | |
dc.date.available | 2022-08-23T15:41:11Z | |
dc.date.issued | 2008-11-13 | |
dc.date.submitted | 2008-12-22 | |
dc.identifier.citation | <p>J Cell Sci. 2008 Dec 1;121(Pt 23):3981-90. Epub 2008 Nov 11. <a href="http://dx.doi.org/10.1242/jcs.033431">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 0021-9533 (Print) | |
dc.identifier.doi | 10.1242/jcs.033431 | |
dc.identifier.pmid | 19001502 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/26574 | |
dc.description.abstract | RUNX1/AML1 is required for definitive hematopoiesis and is frequently targeted by chromosomal translocations in acute myeloid leukemia (AML). The t(8;21)-related AML1-ETO fusion protein blocks differentiation of myeloid progenitors. Here, we show by immunofluorescence microscopy that during interphase, endogenous AML1-ETO localizes to nuclear microenvironments distinct from those containing native RUNX1/AML1 protein. At mitosis, we clearly detect binding of AML1-ETO to nucleolar-organizing regions in AML-derived Kasumi-1 cells and binding of RUNX1/AML1 to the same regions in Jurkat cells. Both RUNX1/AML1 and AML1-ETO occupy ribosomal DNA repeats during interphase, as well as interact with the endogenous RNA Pol I transcription factor UBF1. Promoter cytosine methylation analysis indicates that RUNX1/AML1 binds to rDNA repeats that are more highly CpG methylated than those bound by AML1-ETO. Downregulation by RNA interference reveals that RUNX1/AML1 negatively regulates rDNA transcription, whereas AML1-ETO is a positive regulator in Kasumi-1 cells. Taken together, our findings identify a novel role for the leukemia-related AML1-ETO protein in epigenetic control of cell growth through upregulation of ribosomal gene transcription mediated by RNA Pol I, consistent with the hyper-proliferative phenotype of myeloid cells in AML patients. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19001502&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.title | The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes | |
dc.type | Journal Article | |
dc.source.journaltitle | Journal of cell science | |
dc.source.volume | 121 | |
dc.source.issue | Pt 23 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1079&context=cellbiology_pp&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/cellbiology_pp/80 | |
dc.identifier.contextkey | 686325 | |
refterms.dateFOA | 2022-08-23T15:41:11Z | |
html.description.abstract | <p>RUNX1/AML1 is required for definitive hematopoiesis and is frequently targeted by chromosomal translocations in acute myeloid leukemia (AML). The t(8;21)-related AML1-ETO fusion protein blocks differentiation of myeloid progenitors. Here, we show by immunofluorescence microscopy that during interphase, endogenous AML1-ETO localizes to nuclear microenvironments distinct from those containing native RUNX1/AML1 protein. At mitosis, we clearly detect binding of AML1-ETO to nucleolar-organizing regions in AML-derived Kasumi-1 cells and binding of RUNX1/AML1 to the same regions in Jurkat cells. Both RUNX1/AML1 and AML1-ETO occupy ribosomal DNA repeats during interphase, as well as interact with the endogenous RNA Pol I transcription factor UBF1. Promoter cytosine methylation analysis indicates that RUNX1/AML1 binds to rDNA repeats that are more highly CpG methylated than those bound by AML1-ETO. Downregulation by RNA interference reveals that RUNX1/AML1 negatively regulates rDNA transcription, whereas AML1-ETO is a positive regulator in Kasumi-1 cells. Taken together, our findings identify a novel role for the leukemia-related AML1-ETO protein in epigenetic control of cell growth through upregulation of ribosomal gene transcription mediated by RNA Pol I, consistent with the hyper-proliferative phenotype of myeloid cells in AML patients.</p> | |
dc.identifier.submissionpath | cellbiology_pp/80 | |
dc.contributor.department | Morningside Graduate School of Biomedical Sciences | |
dc.contributor.department | Department of Cell Biology | |
dc.source.pages | 3981-90 |