The histone deacetylase HDAC1 positively regulates Notch signaling during Drosophila wing development.

Zehua Wang,Fang Wang,Zi Nan,Wanzhong Ge,Jiayu Zhang,Qi Zhou,Yongmei Xi,Jialan Lyu,Chen Miao,Xiaohang Yang

doi:10.1242/bio.029637

Abstract

ABSTRACTThe Notch signaling pathway is highly conserved across different animal species and plays crucial roles in development and physiology. Regulation of Notch signaling occurs at multiple levels in different tissues and cell types. Here, we show that the histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during Drosophila wing development. Depletion of HDAC1 causes wing notches on the margin of adult wing. Consistently, the expression of Notch target genes is reduced in the absence of HDAC1 during wing margin formation. We further provide evidence that HDAC1 acts upstream of Notch activation. Mechanistically, we show that HDAC1 regulates Notch protein levels by promoting Notch transcription. Consistent with this, the HDAC1-associated transcriptional co-repressor Atrophin (Atro) is also required for transcriptional activation of Notch in the wing disc. In summary, our results demonstrate that HDAC1 positively regulates Notch signaling and reveal a previously unidentified function of HDAC1 in Notch signaling.

Highlights

HDAC1 regulates Notch signaling in the Drosophila wing Loss of function of HDAC1 is lethal at early larval stages, suggesting that HDAC1 plays an essential role during Drosophila development (Zhu et al, 2008)
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)
It is generally accepted that CSL can recruit the HDAC1 transcriptional co-repressor complex to modify chromatin structure for target gene silencing before Notch activation (Schwanbeck, 2015; Borggrefe and Oswald, 2016)

Summary

Introduction

The Notch pathway is an evolutionarily conserved signaling cascade present in most multicellular organisms, and plays important roles during development and adult life (Bray, 2006; Andersson et al, 2011; Guruharsha et al, 2012). Notch signaling is tightly regulated at multiple levels, including Notch protein modification, trafficking, recycling and degradation (Bray, 2006; Andersson et al, 2011; Guruharsha et al, 2012). It remains largely unexplored how Notch signaling is regulated at the level of Notch receptor transcription

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