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Hematopoietic signaling mechanism revealed from a stem/progenitor cell cistrome
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Hewitt, Kyle J. | - |
dc.contributor.author | Kim, Duk Hyoung | - |
dc.contributor.author | Devadas, Prithvia | - |
dc.contributor.author | Prathibha, Rajalekshmi | - |
dc.contributor.author | Zuo, Chandler | - |
dc.contributor.author | Sanalkumar, Rajendran | - |
dc.contributor.author | Johnson, Kirby D. | - |
dc.contributor.author | Kang, Yoon-A. | - |
dc.contributor.author | Kim, Jin-Soo | - |
dc.contributor.author | Dewey, Colin N. | - |
dc.contributor.author | Keles, Sunduz | - |
dc.contributor.author | Bresnick, Emery H. | - |
dc.date.accessioned | 2020-04-27T12:42:39Z | - |
dc.date.available | 2020-04-27T12:42:39Z | - |
dc.date.created | 2018-11-26 | - |
dc.date.created | 2018-11-26 | - |
dc.date.issued | 2015-07 | - |
dc.identifier.citation | Molecular Cell, Vol.59 No.1, pp.62-74 | - |
dc.identifier.issn | 1097-2765 | - |
dc.identifier.other | 69944 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165648 | - |
dc.description.abstract | Thousands of cis-elements in genomes are predicted to have vital functions. Although conservation, activity in surrogate assays, polymorphisms, and disease mutations provide functional clues, deletion from endogenous loci constitutes the gold-standard test. A GATA-2-binding, Gata2 intronic cis-element (+9.5) required for hematopoietic stem cell genesis in mice is mutated in a human immunodeficiency syndrome. Because +9.5 is the only cis-element known to mediate stem cell genesis, we devised a strategy to identify functionally comparable enhancers ("+9.5-like'') genome-wide. Gene editing revealed +9.5-like activity to mediate GATA-2 occupancy, chromatin opening, and transcriptional activation. A +9.5-like element resided in Samd14, which encodes a protein of unknown function. Samd14 increased hematopoietic progenitor levels/activity and promoted signaling by a pathway vital for hematopoietic stem/progenitor cell regulation (stem cell factor/c-Kit), and c-Kit rescued Samd14 loss-of-function phenotypes. Thus, the hematopoietic stem/progenitor cell cistrome revealed a mediator of a signaling pathway that has broad importance for stem/progenitor cell biology. | - |
dc.language | 영어 | - |
dc.publisher | Cell Press | - |
dc.title | Hematopoietic signaling mechanism revealed from a stem/progenitor cell cistrome | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김진수 | - |
dc.identifier.doi | 10.1016/j.molcel.2015.05.020 | - |
dc.citation.journaltitle | Molecular Cell | - |
dc.identifier.wosid | 000360987300007 | - |
dc.identifier.scopusid | 2-s2.0-84937162292 | - |
dc.citation.endpage | 74 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 62 | - |
dc.citation.volume | 59 | - |
dc.identifier.sci | 000360987300007 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Jin-Soo | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GENOME-WIDE ANALYSIS | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR GATA-2 | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | CHROMATIN OCCUPANCY | - |
dc.subject.keywordPlus | FACTOR COMPLEXES | - |
dc.subject.keywordPlus | DNA ELEMENTS | - |
dc.subject.keywordPlus | MOUSE GENOME | - |
dc.subject.keywordPlus | CIS-ELEMENT | - |
dc.subject.keywordPlus | GENE LOCUS | - |
dc.subject.keywordPlus | PROTEIN | - |
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