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Nucleic Acids Res. 2018 Oct 8. doi: 10.1093/nar/gky892. [Epub ahead of print]

Integrative genomic analysis reveals novel regulatory mechanisms of eyeless during Drosophila eye development.

Yeung K1, Wang F2, Li Y2,3, Wang K2,3, Mardon G1,3,4, Chen R1,2,3,4,5.

Author information

1
Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
2
Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
4
Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
5
Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Abstract

Eyeless (ey) is one of the most critical transcription factors for initiating the entire eye development in Drosophila. However, the molecular mechanisms through which Ey regulates target genes and pathways have not been characterized at the genomic level. Using ChIP-Seq, we generated an endogenous Ey-binding profile in Drosophila developing eyes. We found that Ey binding occurred more frequently at promoter compared to non-promoter regions. Ey promoter binding was correlated with the active transcription of genes involved in development and transcription regulation. An integrative analysis revealed that Ey directly regulated a broad and highly connected genetic network, including many essential patterning pathways, and known and novel eye genes. Interestingly, we observed that Ey could target multiple components of the same pathway, which might enhance its control of these pathways during eye development. In addition to protein-coding genes, we discovered Ey also targeted non-coding RNAs, which represents a new regulatory mechanism employed by Ey. These findings suggest that Ey could use multiple molecular mechanisms to regulate target gene expression and pathway function, which might enable Ey to exhibit a greater flexibility in controlling different processes during eye development.

PMID:
30295802
DOI:
10.1093/nar/gky892

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