Loss of histone deacetylase HDAC1 induces cell death in Drosophila epithelial cells through JNK and Hippo signaling

Abstract

Inactivation of HDAC1 and its homolog HDAC2 or addition of HDAC inhibitors in mammalian systems induces apoptosis, cell cycle arrest, and developmental defects. Although these phenotypes have been extensively characterized, the precise underlying mechanisms remain unclear, particularly in in vivo settings. In this study, we show that inactivation of Rpd3, the only HDAC1 and HDAC2 ortholog in Drosophila, induced apoptosis and clone elimination in the developing eye and wing imaginal discs. Depletion of Rpd3 by RNAi cell-autonomously increased JNK activities and decreased activities of Yki, the nuclear effecter of Hippo signaling pathway. In addition, inhibition of JNK activities largely rescued Rpd3 RNAi-induced apoptosis, but did not affect its inhibition of Yki activities. Conversely, increasing the Yki activities largely rescued Rpd3 RNAi-induced apoptosis, but did not affect its induction of JNK activities. Furthermore, inactivation of Mi-2, a core component of the Rpd3-containing NuRD complex strongly induced JNK activities; while inactivation of Sin3A, a key component of the Rpd3-containing Sin3 complex, significantly inhibited Yki activities. Taken together, these results reveal that inactivation of Rpd3 independently regulates JNK and Yki activities and that both Hippo and JNK signaling pathways contribute to Rpd3 RNAi-induced apoptosis.

The histone deacetylase HDAC1 positively regulates Notch signaling duringDrosophilawing development

“…The data presented here describe the histone deacetylase HDAC1 as a positive regulator of the Notch signaling pathway in Drosophila . Although Drosophila HDAC1 acts broadly to regulate the activity of many signaling pathways, including Hippo, JNK and Hh, our data support a specific interaction between HDAC1 and Notch activity during wing development ( Zhang et al, 2013 , 2016 ).…”

APLP2 Modulates JNK-Dependent Cell Migration inDrosophila

“…We noticed that patched -Gal4 ( Figures 1(A) – 1(A”) ) driven expression of APLP2 in the wing disc produced a dosage-dependent invasive phenotype with GFP-labelled cells diverted from the A/P boundary to the posterior part ( Figures 1(B) – 1(B”) , 1(E) , Figure S1 ), while expression of LacZ failed to induce such phenotypes ( Figures 1(D) – 1(D”) , and 1(E) ). The c-Jun N-Terminal Protein Kinase (JNK) signaling has been implicated in a wide range of cellular functions including cell death and migration [ 32 , 36 – 40 ]. Consistently, RNAi-mediated depletion of puckered ( puc ), a negative regulator of JNK signaling [ 41 , 42 ], promoted a cell migrating phenotype ( Figures 1(C) – 1(C”) , and 1(E) ).…”

Genome-Wide Expression Analysis of Long Noncoding RNAs and Their Target Genes in Metafemale Drosophila

“…Sin3A is a large scaffold protein that modifies chromatin structure by recruiting histone deacetylases and other transcription factors, thereby regulating gene expression [47]. It is a genome-wide transcriptional regulator with the ability to positively or negatively regulate the expression of various genes and thus participate in the regulation of various biological processes, including cell proliferation, differentiation, apoptosis and cell cycle progression, and it is related to various signaling pathways, such as the Hippo and JNK pathways [60,61]. MED1 is one of the components of the multiprotein mediator complex, which mediates the action of gene-specific transcription factors at enhancers and the transcriptional mechanism of RNA polymerase II (RNAPII) at promoters.…”