Abstract
Juvenile hormones (JH) and ecdysone coordinately regulate metamorphosis in Aedes aegypti. We studied the function of an epigenetic regulator and multifunctional transactivator, CREB binding protein (CBP) in A. aegypti. RNAi-mediated knockdown of CBP in Ae. aegypti larvae resulted in suppression of JH primary response gene, Krüppel-homolog 1 (Kr-h1), and induction of primary ecdysone response gene, E93, resulting in multiple effects including early metamorphosis, larval-pupal intermediate formation, mortality and inhibition of compound eye development. RNA sequencing identified hundreds of genes, including JH and ecdysone response genes regulated by CBP. In the presence of JH, CBP upregulates Kr-h1 by acetylating core histones at the Kr-h1 promoter and facilitating the recruitment of JH receptor and other proteins. CBP suppresses metamorphosis regulators, EcR-A, USP-A, BR-C, and E93 through the upregulation of Kr-h1 and E75A. CBP regulates the expression of core eye specification genes including those involved in TGF-β and EGFR signaling. These studies demonstrate that CBP is an essential player in JH and 20E action and regulates metamorphosis and compound eye development in Ae. aegypti.
| Original language | English |
|---|---|
| Article number | 194576 |
| Journal | Biochimica et Biophysica Acta - Gene Regulatory Mechanisms |
| Volume | 1863 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2020 |
Bibliographical note
Publisher Copyright:© 2020 Elsevier B.V.
Funding
We thank the freelance writers, K.P. Madhu and Gita Madhu, for their valuable comments and suggestions on the manuscript. This work was supported by grant a grant from NIH (GM070559-14) to S.R.P. We thank S.R.P. lab members, Xien Chen and Kim Kyungbo for providing AaE75A and AaKr-h1 plasmid constructs. The RNA sequencing data have been deposited to the National Center for Biotechnology Information's (NCBI) Sequence Read Archive (SRA) with accession number PRJNA591192. S.R.P. and S.C.G. designed research; S.C.G. and R.K.D. performed research; S.C.G. analyzed data; S.C.G. and S.R.P. wrote the paper. We thank the freelance writers, K.P. Madhu and Gita Madhu, for their valuable comments and suggestions on the manuscript. This work was supported by grant a grant from NIH ( GM070559-14 ) to S.R.P. We thank S.R.P. lab members, Xien Chen and Kim Kyungbo for providing AaE75A and AaKr-h1 plasmid constructs.
| Funders | Funder number |
|---|---|
| National Center for Biotechnology Information's | PRJNA591192 |
| National Institutes of Health (NIH) | |
| National Institute of General Medical Sciences | R01GM070559 |
Keywords
- Acetylation
- CBP
- Ecdysone
- Epigenetics
- Juvenile hormone
- Kr-h1, E93
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics