| http://purl.uniprot.org/citations/31120998 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31120998 | http://www.w3.org/2000/01/rdf-schema#comment | "C/EBPα plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPα-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0217604"xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Guo H."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Ma P."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Peng L."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Hess J.L."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Friedman A.D."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Aplan P.D."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/author | "Dennison L."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/pages | "e0217604"xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/title | "HoxA9 binds and represses the Cebpa +8 kb enhancer."xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://purl.uniprot.org/core/volume | "14"xsd:string |
| http://purl.uniprot.org/citations/31120998 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31120998 |
| http://purl.uniprot.org/citations/31120998 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31120998 |
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| http://purl.uniprot.org/uniprot/#_P53566-mappedCitation-31120998 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31120998 |
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| http://purl.uniprot.org/uniprot/Q3U2H8 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31120998 |
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| http://purl.uniprot.org/uniprot/P53566 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31120998 |