Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner.
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 o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3715461?pdf=render |
| _version_ | 1818510835205537792 |
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| author | Paejonette T Jacobs Li Cao Jeremy B Samon Christyne A Kane Emmett E Hedblom Anne Bowcock Janice C Telfer |
| author_facet | Paejonette T Jacobs Li Cao Jeremy B Samon Christyne A Kane Emmett E Hedblom Anne Bowcock Janice C Telfer |
| author_sort | Paejonette T Jacobs |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T23:25:31Z |
| format | Article |
| id | doaj.art-cb430012d683438ea289c8bef9f74855 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:25:31Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cb430012d683438ea289c8bef9f748552022-12-22T01:29:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6908310.1371/journal.pone.0069083Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner.Paejonette T JacobsLi CaoJeremy B SamonChristyne A KaneEmmett E HedblomAnne BowcockJanice C TelferThe 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.http://europepmc.org/articles/PMC3715461?pdf=render |
| spellingShingle | Paejonette T Jacobs Li Cao Jeremy B Samon Christyne A Kane Emmett E Hedblom Anne Bowcock Janice C Telfer Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. PLoS ONE |
| title | Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. |
| title_full | Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. |
| title_fullStr | Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. |
| title_full_unstemmed | Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. |
| title_short | Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. |
| title_sort | runx transcription factors repress human and murine c myc expression in a dna binding and c terminally dependent manner |
| url | http://europepmc.org/articles/PMC3715461?pdf=render |
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