Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/98553
Title: Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish
Authors: Wang, Xingang
Zhao, Zhonghua
Muller, Julius
Iyu, Audrey
Khng, Alexis Jiaying
Guccione, Ernesto
Ruan, Yijun
Ingham, Philip William
Issue Date: 2013
Source: 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.
Series/Report no.: Biology Open
Abstract: 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.
URI: https://hdl.handle.net/10356/98553
http://hdl.handle.net/10220/38599
ISSN: 2046-6390
DOI: 10.1242/bio.20136262
Rights: © 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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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