The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus.
The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of...
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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: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054935&type=printable |
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| author | Kristin A Sauter M Amine Bouhlel Julie O'Neal David P Sester Hiromi Tagoh Richard M Ingram Clare Pridans Constanze Bonifer David A Hume |
| author_facet | Kristin A Sauter M Amine Bouhlel Julie O'Neal David P Sester Hiromi Tagoh Richard M Ingram Clare Pridans Constanze Bonifer David A Hume |
| author_sort | Kristin A Sauter |
| collection | DOAJ |
| description | The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element. |
| format | Article |
| id | doaj-art-eb2575a40a6e4190aca50dcc8f48a83a |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-eb2575a40a6e4190aca50dcc8f48a83a2025-08-20T03:09:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5493510.1371/journal.pone.0054935The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus.Kristin A SauterM Amine BouhlelJulie O'NealDavid P SesterHiromi TagohRichard M IngramClare PridansConstanze BoniferDavid A HumeThe gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054935&type=printable |
| spellingShingle | Kristin A Sauter M Amine Bouhlel Julie O'Neal David P Sester Hiromi Tagoh Richard M Ingram Clare Pridans Constanze Bonifer David A Hume The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus. PLoS ONE |
| title | The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus. |
| title_full | The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus. |
| title_fullStr | The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus. |
| title_full_unstemmed | The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus. |
| title_short | The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus. |
| title_sort | function of the conserved regulatory element within the second intron of the mammalian csf1r locus |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054935&type=printable |
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