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

Author:

Wang Zehua123,Lyu Jialan12ORCID,Wang Fang3,Miao Chen12,Nan Zi3ORCID,Zhang Jiayu4,Xi Yongmei12,Zhou Qi4,Yang Xiaohang12,Ge Wanzhong12ORCID

Affiliation:

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, 310058, China

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.

Funder

National Natural Science Foundation of China

Ministry of Science and Technology of the People's Republic of China

Publisher

The Company of Biologists

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology

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