Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes
Histone H3 lysine 4 (H3K4) methylation is generally recognized as a prominent marker of gene activation. While Set1/Mll complexes are major methyltransferases that are responsible for H3K4 methylation, the mechanism of how these complexes are recruited into the target gene promotor is still unclear....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | European Journal of Cell Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933523000109 |
| _version_ | 1797799052148998144 |
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| author | Zhe Liu Weijing Hu Yali Qin Li Sun Lingyun Jing Manman Lu Yan Li Jing Qu Zhenhua Yang |
| author_facet | Zhe Liu Weijing Hu Yali Qin Li Sun Lingyun Jing Manman Lu Yan Li Jing Qu Zhenhua Yang |
| author_sort | Zhe Liu |
| collection | DOAJ |
| description | Histone H3 lysine 4 (H3K4) methylation is generally recognized as a prominent marker of gene activation. While Set1/Mll complexes are major methyltransferases that are responsible for H3K4 methylation, the mechanism of how these complexes are recruited into the target gene promotor is still unclear. Here, starting with an affinity purification-mass spectrometry approach, we have found that Isl1, a highly tissue-specific expressed LIM/homeodomain transcription factor, is physically associated with Set1/Mll complexes. We then show that Wdr5 directly binds to Isl1. And this binding is likely mediated by the homeodomain of Isl1. Functionally, using mouse β-cell and human neuroblastoma tumor cell lines, we show that both Wdr5 binding and H3K4 methylation level at promoters of some Isl1 target genes are significantly reduced upon depletion of Isl1, suggesting Isl1 is required for efficient locus-specific H3K4 methylation. Taken together, our results establish a critical role of Set1/Mll complexes in regulating the target gene expression of Isl1. |
| first_indexed | 2024-03-13T04:14:09Z |
| format | Article |
| id | doaj.art-00ddbd7dd33c48e28607f44ee5269ec1 |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2024-03-13T04:14:09Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-00ddbd7dd33c48e28607f44ee5269ec12023-06-21T06:50:53ZengElsevierEuropean Journal of Cell Biology0171-93352023-06-011022151295Isl1 promotes gene transcription through physical interaction with Set1/Mll complexesZhe Liu0Weijing Hu1Yali Qin2Li Sun3Lingyun Jing4Manman Lu5Yan Li6Jing Qu7Zhenhua Yang8School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaSchool of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaCorresponding authors.; School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaCorresponding authors.; School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaHistone H3 lysine 4 (H3K4) methylation is generally recognized as a prominent marker of gene activation. While Set1/Mll complexes are major methyltransferases that are responsible for H3K4 methylation, the mechanism of how these complexes are recruited into the target gene promotor is still unclear. Here, starting with an affinity purification-mass spectrometry approach, we have found that Isl1, a highly tissue-specific expressed LIM/homeodomain transcription factor, is physically associated with Set1/Mll complexes. We then show that Wdr5 directly binds to Isl1. And this binding is likely mediated by the homeodomain of Isl1. Functionally, using mouse β-cell and human neuroblastoma tumor cell lines, we show that both Wdr5 binding and H3K4 methylation level at promoters of some Isl1 target genes are significantly reduced upon depletion of Isl1, suggesting Isl1 is required for efficient locus-specific H3K4 methylation. Taken together, our results establish a critical role of Set1/Mll complexes in regulating the target gene expression of Isl1.http://www.sciencedirect.com/science/article/pii/S0171933523000109H3K4 methylationSet1/Mll complexesIsl1Gene expression |
| spellingShingle | Zhe Liu Weijing Hu Yali Qin Li Sun Lingyun Jing Manman Lu Yan Li Jing Qu Zhenhua Yang Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes European Journal of Cell Biology H3K4 methylation Set1/Mll complexes Isl1 Gene expression |
| title | Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes |
| title_full | Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes |
| title_fullStr | Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes |
| title_full_unstemmed | Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes |
| title_short | Isl1 promotes gene transcription through physical interaction with Set1/Mll complexes |
| title_sort | isl1 promotes gene transcription through physical interaction with set1 mll complexes |
| topic | H3K4 methylation Set1/Mll complexes Isl1 Gene expression |
| url | http://www.sciencedirect.com/science/article/pii/S0171933523000109 |
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