DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study
CCCTC-binding factor (CTCF) is a zinc-finger protein, serving an important part in the genome architecture as well as some biochemical processes. Over 70,000 CTCF binding DNA sites have been detected genome-wide, and most anchors of chromatin loops are demarcated with the CTCF binding. Various prote...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-10-01
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| Series: | Acta Pharmaceutica Sinica B |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383518301990 |
| _version_ | 1818352637509107712 |
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| author | Jingjing Guo Ni Li Jiexiong Han Fei Pei Tianyu Wang Duo Lu Jiandong Jiang |
| author_facet | Jingjing Guo Ni Li Jiexiong Han Fei Pei Tianyu Wang Duo Lu Jiandong Jiang |
| author_sort | Jingjing Guo |
| collection | DOAJ |
| description | CCCTC-binding factor (CTCF) is a zinc-finger protein, serving an important part in the genome architecture as well as some biochemical processes. Over 70,000 CTCF binding DNA sites have been detected genome-wide, and most anchors of chromatin loops are demarcated with the CTCF binding. Various protein or RNA molecules interact with DNA-bound CTCF to conduct different biological functions, and potentially the interfaces between CTCF and its cofactors can be targets for drug development. Here we identify the effective region of CTCF in DNA recognition, which defines the exposed CTCF surface feature for the interaction of cofactors. While the zinc-finger region contributes the most in DNA association, its binding affinity varies based on different DNA sequences. To investigate the effectiveness of individual zinc-fingers, the key residues are mutated to inactivate the DNA binding ability, while the finger configuration and the spacing between fingers are preserved. The strategy is proved to be successful, while clear differences are observed in the DNA binding affinities among the 11 finger mutants and the result is consistent to previous studies in general. With the help of inactivated finger mutants, we identify the ineffective fingers and the dominant effective fingers, which form distinctive patterns on different DNA targets. KEY WORDS: CTCF, Zinc-finger, Structure integrity, Mutagenesis, DNA recognition patterns |
| first_indexed | 2024-12-13T18:56:48Z |
| format | Article |
| id | doaj.art-7638b998a62345f8afca89cf269cb577 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-13T18:56:48Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-7638b998a62345f8afca89cf269cb5772022-12-21T23:34:47ZengElsevierActa Pharmaceutica Sinica B2211-38352018-10-0186900908DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis studyJingjing Guo0Ni Li1Jiexiong Han2Fei Pei3Tianyu Wang4Duo Lu5Jiandong Jiang6State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaCorresponding authors. Tel.: +86 10 63039979; fax: +86 10 63017757.; State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaCorresponding authors. Tel.: +86 10 63039979; fax: +86 10 63017757.; State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaCCCTC-binding factor (CTCF) is a zinc-finger protein, serving an important part in the genome architecture as well as some biochemical processes. Over 70,000 CTCF binding DNA sites have been detected genome-wide, and most anchors of chromatin loops are demarcated with the CTCF binding. Various protein or RNA molecules interact with DNA-bound CTCF to conduct different biological functions, and potentially the interfaces between CTCF and its cofactors can be targets for drug development. Here we identify the effective region of CTCF in DNA recognition, which defines the exposed CTCF surface feature for the interaction of cofactors. While the zinc-finger region contributes the most in DNA association, its binding affinity varies based on different DNA sequences. To investigate the effectiveness of individual zinc-fingers, the key residues are mutated to inactivate the DNA binding ability, while the finger configuration and the spacing between fingers are preserved. The strategy is proved to be successful, while clear differences are observed in the DNA binding affinities among the 11 finger mutants and the result is consistent to previous studies in general. With the help of inactivated finger mutants, we identify the ineffective fingers and the dominant effective fingers, which form distinctive patterns on different DNA targets. KEY WORDS: CTCF, Zinc-finger, Structure integrity, Mutagenesis, DNA recognition patternshttp://www.sciencedirect.com/science/article/pii/S2211383518301990 |
| spellingShingle | Jingjing Guo Ni Li Jiexiong Han Fei Pei Tianyu Wang Duo Lu Jiandong Jiang DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study Acta Pharmaceutica Sinica B |
| title | DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study |
| title_full | DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study |
| title_fullStr | DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study |
| title_full_unstemmed | DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study |
| title_short | DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study |
| title_sort | dna recognition patterns of the multi zinc finger protein ctcf a mutagenesis study |
| url | http://www.sciencedirect.com/science/article/pii/S2211383518301990 |
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