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dc.contributor.authorKerenyi, Marc Aen_US
dc.contributor.authorShao, Zhenen_US
dc.contributor.authorHsu, Yu-Jungen_US
dc.contributor.authorGuo, Guojien_US
dc.contributor.authorLuc, Sidinhen_US
dc.contributor.authorO'Brien, Kassandraen_US
dc.contributor.authorFujiwara, Yukoen_US
dc.contributor.authorPeng, Congen_US
dc.contributor.authorNguyen, Minhen_US
dc.contributor.authorOrkin, Stuart Hen_US
dc.date.accessioned2014-02-13T19:01:48Z
dc.date.issued2013en_US
dc.identifier.citationKerenyi, Marc A, Zhen Shao, Yu-Jung Hsu, Guoji Guo, Sidinh Luc, Kassandra O'Brien, Yuko Fujiwara, Cong Peng, Minh Nguyen, and Stuart H Orkin. 2013. “Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation.” eLife 2 (1): e00633. doi:10.7554/eLife.00633. http://dx.doi.org/10.7554/eLife.00633.en
dc.identifier.issn2050-084Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11708622
dc.description.abstractHere, we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys4 or Lys9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis, combining global occupancy of Lsd1, genome-wide analysis of its substrates H3K4 monomethylation and dimethylation, and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We found that Lsd1 acts at transcription start sites, as well as enhancer regions. Loss of Lsd1 was associated with increased H3K4me1 and H3K4me2 methylation on HSPC genes and gene derepression. Failure to fully silence HSPC genes compromised differentiation of hematopoietic stem cells as well as mature blood cell lineages. Collectively, our data indicate that Lsd1-mediated concurrent repression of enhancer and promoter activity of stem and progenitor cell genes is a pivotal epigenetic mechanism required for proper hematopoietic maturation. DOI: http://dx.doi.org/10.7554/eLife.00633.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.00633en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687337/pdf/en
dash.licenseLAAen_US
dc.subjecthistone demethylaseen
dc.subjectLsd1en
dc.subjectKDM1en
dc.subjectHSCen
dc.subjectgranulocyteen
dc.subjectenhanceren
dc.subjectMouseen
dc.titleHistone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorGuo, Guojien_US
dc.date.available2014-02-13T19:01:48Z
dc.identifier.doi10.7554/eLife.00633*
dash.contributor.affiliatedLuc, Sidinh
dash.contributor.affiliatedNguyen, Minh
dash.contributor.affiliatedPeng, Cong
dash.contributor.affiliatedGuo, Guoji
dash.contributor.affiliatedOrkin, Stuart
dash.contributor.affiliatedFujiwara, Yuko


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