A new pipeline SPICE identifies novel JUN-IKZF1 composite elements
Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partne...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/88833 |
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| _version_ | 1841551654060556288 |
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| author | Peng Li Sree Pulugulla Sonali Das Jangsuk Oh Rosanne Spolski Jian-Xin Lin Warren J Leonard |
| author_facet | Peng Li Sree Pulugulla Sonali Das Jangsuk Oh Rosanne Spolski Jian-Xin Lin Warren J Leonard |
| author_sort | Peng Li |
| collection | DOAJ |
| description | Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements. One such novel interaction was identified at CNS9, an upstream conserved noncoding region in the human IL10 gene, which harbors a non-canonical IKZF1 binding site. We confirmed the cooperative binding of JUN and IKZF1 and showed that the activity of an IL10-luciferase reporter construct in primary B and T cells depended on both this site and the AP1 binding site within this composite element. Overall, our findings reveal an unappreciated global association of IKZF1 and AP1 and establish SPICE as a valuable new pipeline for predicting novel transcription binding complexes. |
| format | Article |
| id | doaj-art-d21fc3ec79c740edb907ebe66d15a806 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-d21fc3ec79c740edb907ebe66d15a8062025-01-09T15:58:52ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011210.7554/eLife.88833A new pipeline SPICE identifies novel JUN-IKZF1 composite elementsPeng Li0https://orcid.org/0000-0002-4721-5936Sree Pulugulla1Sonali Das2Jangsuk Oh3Rosanne Spolski4Jian-Xin Lin5Warren J Leonard6https://orcid.org/0000-0002-5740-7448Amgen Inc, Rockville, United StatesLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, United StatesLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, United StatesLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, United StatesLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, United StatesLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, United StatesLaboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, United StatesTranscription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements. One such novel interaction was identified at CNS9, an upstream conserved noncoding region in the human IL10 gene, which harbors a non-canonical IKZF1 binding site. We confirmed the cooperative binding of JUN and IKZF1 and showed that the activity of an IL10-luciferase reporter construct in primary B and T cells depended on both this site and the AP1 binding site within this composite element. Overall, our findings reveal an unappreciated global association of IKZF1 and AP1 and establish SPICE as a valuable new pipeline for predicting novel transcription binding complexes.https://elifesciences.org/articles/88833Protein-DNAIKZF1SPICEJUNAP1IL-21 |
| spellingShingle | Peng Li Sree Pulugulla Sonali Das Jangsuk Oh Rosanne Spolski Jian-Xin Lin Warren J Leonard A new pipeline SPICE identifies novel JUN-IKZF1 composite elements eLife Protein-DNA IKZF1 SPICE JUN AP1 IL-21 |
| title | A new pipeline SPICE identifies novel JUN-IKZF1 composite elements |
| title_full | A new pipeline SPICE identifies novel JUN-IKZF1 composite elements |
| title_fullStr | A new pipeline SPICE identifies novel JUN-IKZF1 composite elements |
| title_full_unstemmed | A new pipeline SPICE identifies novel JUN-IKZF1 composite elements |
| title_short | A new pipeline SPICE identifies novel JUN-IKZF1 composite elements |
| title_sort | new pipeline spice identifies novel jun ikzf1 composite elements |
| topic | Protein-DNA IKZF1 SPICE JUN AP1 IL-21 |
| url | https://elifesciences.org/articles/88833 |
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