title: Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner.
abstract: The transcription factors Runx1 and c-Myc have individually been shown to regulate important gene targets as well as to collaborate in oncogenesis. However, it is unknown whether there is a regulatory relationship between the two genes. In this study, we investigated the transcriptional regulation of endogenous c-Myc by Runx1 in the human T cell line Jurkat and murine primary hematopoietic cells. Endogenous Runx1 binds to multiple sites in the c-Myc locus upstream of the c-Myc transcriptional start site. Cells transduced with a C-terminally truncated Runx1 (Runx1.d190), which lacks important cofactor interaction sites and can block C-terminal-dependent functions of all Runx transcription factors, showed increased transcription of c-Myc. In order to monitor c-Myc expression in response to early and transiently-acting Runx1.d190, we generated a cell membrane-permeable TAT-Runx1.d190 fusion protein. Murine splenocytes treated with TAT-Runx1.d190 showed an increase in the transcription of c-Myc within 2 hours, peaking at 4 hours post-treatment and declining thereafter. This effect is dependent on the ability of Runx1.d190 to bind to DNA. The increase in c-Myc transcripts is correlated with increased c-Myc protein levels. Collectively, these data show that Runx1 directly regulates c-Myc transcription in a C-terminal- and DNA-binding-dependent manner.
authors.affiliation: Program in Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
authors.forename: Paejonette T
authors.initials: PT
authors.lastname: Jacobs
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Samon
authors.forename: Christyne A
authors.initials: CA
authors.lastname: Kane
authors.forename: Emmett E
authors.initials: EE
authors.lastname: Hedblom
authors.forename: Anne
authors.initials: A
authors.lastname: Bowcock
authors.forename: Janice C
authors.initials: JC
authors.lastname: Telfer
mesh_terms: D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D015696:Gene Products, tat / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D016296:Mutagenesis; D010957:Plasmids / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D015696:Gene Products, tat; D016271:Proto-Oncogene Proteins c-myc; C493728:RUNX1 protein, human; D011993:Recombinant Fusion Proteins; D004247:DNA