2011
DOI: 10.1038/emboj.2011.285
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RUNX1 regulates theCD34gene in haematopoietic stem cells by mediating interactions with a distal regulatory element

Abstract: The transcription factor RUNX1 is essential to establish the haematopoietic gene expression programme; however, the mechanism of how it activates transcription of haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel insights into RUNX1 function by studying regulation of the human CD34 gene, which is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs, we identified a novel downstream regulatory element (DRE), which is bound by RUNX1 and is necessary for human C… Show more

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Cited by 29 publications
(20 citation statements)
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“…However, these data did not answer the question of whether CTCF binding or other mechanisms would mediate loop formation. Importantly, we recently described that targeted mutations of RUNX binding sites in a downstream regulatory element (DRE) of a human CD34 transgene caused the perturbation of the DRE-promoter interaction in transgenic mice (Levantini et al, 2011). Along with the functional models presented here, specific disruption of PU.1 binding in the URE of the endogenous PU.1 locus can be used to distinguish between correlation and causation of the transcription factor binding and chromosome looping necessary for gene activation.…”
Section: Discussionmentioning
confidence: 99%
“…However, these data did not answer the question of whether CTCF binding or other mechanisms would mediate loop formation. Importantly, we recently described that targeted mutations of RUNX binding sites in a downstream regulatory element (DRE) of a human CD34 transgene caused the perturbation of the DRE-promoter interaction in transgenic mice (Levantini et al, 2011). Along with the functional models presented here, specific disruption of PU.1 binding in the URE of the endogenous PU.1 locus can be used to distinguish between correlation and causation of the transcription factor binding and chromosome looping necessary for gene activation.…”
Section: Discussionmentioning
confidence: 99%
“…However, formation of such three-dimensional chromatin structures must be tightly controlled to participate in the dynamic regulation of gene expression. Indeed, several lineage-specific hematopoietic TFs, such as PU.1 and Runx1, have been shown to facilitate DNA looping (Levantini et al, 2011;Schonheit et al, 2013;Staber et al, 2013).…”
Section: Pu1 and The Three-dimensional Chromatin Structurementioning
confidence: 99%
“…Although expression of all Runx genes was clearly detectable in both populations, Runx1 was the most highly expressed factor in HSCs ( Figure 1A) (note that expression data for Runx1 have been presented in Levantini et al, 33 see supplemental Figure 1). To test whether loss of Runx1 would result in a compensatory upregulation of either Runx2 or Runx3 in HSCs, we used Mx1-Cre1 inducible Runx1 knockout mice 26 and tested changes in messenger RNA (mRNA) levels of individual Runx factors.…”
Section: Runx Binding Sites In the Pu1 Ure Mediate Pu1 Transcriptiomentioning
confidence: 99%