Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks
The revolutionary CRISPR-Cas9 genome engineering technology has been repurposed into a docking tool by fusing various effector proteins to the catalytically inactive Cas9. The modified system can regulate transcription by editing the epigenetic code, thereby modifying the local chromatin structure....
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/80404 http://hdl.handle.net/10220/46576 |
| _version_ | 1811688041348071424 |
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| author | Loh, Xinpeng |
| author2 | Amartya Sanyal |
| author_facet | Amartya Sanyal Loh, Xinpeng |
| author_sort | Loh, Xinpeng |
| collection | NTU |
| description | The revolutionary CRISPR-Cas9 genome engineering technology has been repurposed into a docking tool by fusing various effector proteins to the catalytically inactive Cas9. The modified system can regulate transcription by editing the epigenetic code, thereby modifying the local chromatin structure. While several reports have harnessed the potential of the CRISPR interference (CRISPRi) system to silence genes, only limited types of effector domains have been tested to date. Here, we expanded the repertoire of effector domains in the CRISPRi toolbox by incorporating novel epigenetic modulators - Histone Deacetylase 1 and Heterochromatin Protein 1 alpha - to study gene regulatory networks (GRNs). Efficiencies of these novel epigenetic effector domains were successfully demonstrated by targeting enhancers of globin genes in leukemia cells, as well as drug resistance genes in a chemoresistant model. Integration of new epigenetic modulators with CRISPRi would present new possibilities for understanding GRNs in various cell types and context. |
| first_indexed | 2024-10-01T05:25:54Z |
| format | Thesis |
| id | ntu-10356/80404 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:25:54Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/804042023-02-28T18:40:39Z Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks Loh, Xinpeng Amartya Sanyal School of Biological Sciences DRNTU::Science::Biological sciences The revolutionary CRISPR-Cas9 genome engineering technology has been repurposed into a docking tool by fusing various effector proteins to the catalytically inactive Cas9. The modified system can regulate transcription by editing the epigenetic code, thereby modifying the local chromatin structure. While several reports have harnessed the potential of the CRISPR interference (CRISPRi) system to silence genes, only limited types of effector domains have been tested to date. Here, we expanded the repertoire of effector domains in the CRISPRi toolbox by incorporating novel epigenetic modulators - Histone Deacetylase 1 and Heterochromatin Protein 1 alpha - to study gene regulatory networks (GRNs). Efficiencies of these novel epigenetic effector domains were successfully demonstrated by targeting enhancers of globin genes in leukemia cells, as well as drug resistance genes in a chemoresistant model. Integration of new epigenetic modulators with CRISPRi would present new possibilities for understanding GRNs in various cell types and context. Master of Science 2018-11-07T12:37:05Z 2019-12-06T13:48:42Z 2018-11-07T12:37:05Z 2019-12-06T13:48:42Z 2018 Thesis Loh, X. (2018). Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks. Master's thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/80404 http://hdl.handle.net/10220/46576 10.32657/10220/46576 en 75 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Loh, Xinpeng Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks |
| title | Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks |
| title_full | Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks |
| title_fullStr | Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks |
| title_full_unstemmed | Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks |
| title_short | Effect of CRISPR-based epigenetic interference on cis-regulatory gene networks |
| title_sort | effect of crispr based epigenetic interference on cis regulatory gene networks |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/80404 http://hdl.handle.net/10220/46576 |
| work_keys_str_mv | AT lohxinpeng effectofcrisprbasedepigeneticinterferenceoncisregulatorygenenetworks |