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

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

doi:10.1242/bio.029637

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

Biol Open. 2018 Feb 20;7(2):bio029637. doi: 10.1242/bio.029637.

Authors

Zehua Wang^{1

2

3}, Jialan Lyu^{1

2}, Fang Wang³, Chen Miao^{1

2}, Zi Nan³, Jiayu Zhang⁴, Yongmei Xi^{1

2}, Qi Zhou⁴, Xiaohang Yang^{1

2}, Wanzhong Ge^{5

2}

Affiliations

¹ Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
² Institute of Genetics and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
³ College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
⁴ Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
⁵ Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China wanzhongge@zju.edu.cn.

Abstract

The 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.

Keywords: Atrophin; Drosophila wing development; HDAC1; Notch.