Juvenile hormone-induced histone deacetylase 3 suppresses apoptosis to maintain larval midgut in the yellow fever mosquito

Sharath Chandra Gaddelapati, Najla M. Albishi, Ramesh Kumar Dhandapani, Subba Reddy Palli

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The yellow fever mosquito, Aedes aegypti, is distributed worldwide and transmits viruses that cause many diseases, including dengue, yellow fever, chikungunya, and zika. Epigenetic modifications such as acetylation of histones regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) control insect development. We recently reported that the Creb-binding protein (a HAT) regulates the metamorphosis of A. aegypti. However, the function of HDACs in A. aegypti is not known. In this study, we identified 10 genes coding for HDACs in A. aegypti and determined their function in larval development using RNA interference (RNAi). Knockdown of each HDAC has a distinct effect on the growth, development, and metamorphosis of A. aegypti. Knockdown of HDAC3 severely affected the larval survival, indicating its indispensable role in larval development. HDAC3 is highly expressed during the larval stages, and its messenger RNA (mRNA) levels correlate with the juvenile hormone (JH) titers. JH induces the expression of HDAC3 through its receptor, methoprene-tolerant (Met). Knockdown of HDAC3 resulted in increased expression of proapoptotic genes involved in apoptosis of larval midgut cells. This consequently decreased midgut size and led to larval death. HDAC3 deacetylates histone H4 localized at the promoters of proapoptotic genes and suppresses their expression. In addition, a corepressor, SMRTER, is required for HDAC3-mediated suppression of proapoptotic genes. Interestingly, ecdysone attenuates HDAC3-mediated repression of proapoptotic genes. These data demonstrate that JH-induced HDAC3 is a key player in JH suppression of precocious larval cell death and metamorphosis in A. aegypti.

Original languageEnglish
Article numbere2118871119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number11
DOIs
StatePublished - Mar 15 2022

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. This work was supported by a grant from NIH (GM070559) to S.R.P. Thanks to Dr. Xien Chen and Dr. Kim Kyungbo for providing plasmid constructs and Dr. Guan-Heng Zhu for providing the EGFP-DsRed–expressing transgenic line of A. aegypti. We also thank Jeff Howell for help with insect-rearing and editing the manuscript.

Publisher Copyright:
© 2022 National Academy of Sciences. All rights reserved.

Keywords

  • Aedes aegypti
  • apoptosis
  • epigenetics
  • histone deacetylase
  • midgut-remodeling

ASJC Scopus subject areas

  • General

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