Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish
Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/98553 http://hdl.handle.net/10220/38599 |
| _version_ | 1826122169803866112 |
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| author | Wang, Xingang Zhao, Zhonghua Muller, Julius Iyu, Audrey Khng, Alexis Jiaying Guccione, Ernesto Ruan, Yijun Ingham, Philip William |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Wang, Xingang Zhao, Zhonghua Muller, Julius Iyu, Audrey Khng, Alexis Jiaying Guccione, Ernesto Ruan, Yijun Ingham, Philip William |
| author_sort | Wang, Xingang |
| collection | NTU |
| description | Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a. |
| first_indexed | 2024-10-01T05:44:06Z |
| format | Journal Article |
| id | ntu-10356/98553 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:44:06Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/985532022-02-16T16:28:48Z Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish Wang, Xingang Zhao, Zhonghua Muller, Julius Iyu, Audrey Khng, Alexis Jiaying Guccione, Ernesto Ruan, Yijun Ingham, Philip William Lee Kong Chian School of Medicine (LKCMedicine) Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2015-09-04T07:11:19Z 2019-12-06T19:56:46Z 2015-09-04T07:11:19Z 2019-12-06T19:56:46Z 2013 2013 Journal Article Wang, X., Zhao, Z., Muller, J., Iyu, A., Khng, A. J., Guccione, E., et al. (2013). Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish. Biology Open, 2(11), 1203-1213. 2046-6390 https://hdl.handle.net/10356/98553 http://hdl.handle.net/10220/38599 10.1242/bio.20136262 24244857 en Biology Open © 2013. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. application/pdf |
| spellingShingle | Wang, Xingang Zhao, Zhonghua Muller, Julius Iyu, Audrey Khng, Alexis Jiaying Guccione, Ernesto Ruan, Yijun Ingham, Philip William Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish |
| title | Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish |
| title_full | Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish |
| title_fullStr | Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish |
| title_full_unstemmed | Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish |
| title_short | Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish |
| title_sort | targeted inactivation and identification of targets of the gli2a transcription factor in the zebrafish |
| url | https://hdl.handle.net/10356/98553 http://hdl.handle.net/10220/38599 |
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