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

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          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.

          Abstract

          Summary: The histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during Drosophila wing development, and its depletion causes wing notches on the margin of adult wing.

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          Most cited references33

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          The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men.

          Protein lysine deacetylases have a pivotal role in numerous biological processes and can be divided into the Rpd3/Hda1 and sirtuin families, each having members in diverse organisms including prokaryotes. In vertebrates, the Rpd3/Hda1 family contains 11 members, traditionally referred to as histone deacetylases (HDAC) 1-11, which are further grouped into classes I, II and IV. Whereas most class I HDACs are subunits of multiprotein nuclear complexes that are crucial for transcriptional repression and epigenetic landscaping, class II members regulate cytoplasmic processes or function as signal transducers that shuttle between the cytoplasm and the nucleus. Little is known about class IV HDAC11, although its evolutionary conservation implies a fundamental role in various organisms.
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            Histone acetylation and transcriptional regulatory mechanisms.

            K Struhl (1998)
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              The Varied Roles of Notch in Cancer.

              Notch receptors influence cellular behavior by participating in a seemingly simple signaling pathway, but outcomes produced by Notch signaling are remarkably varied depending on signal dose and cell context. Here, after briefly reviewing new insights into physiologic mechanisms of Notch signaling in healthy tissues and defects in Notch signaling that contribute to congenital disorders and viral infection, we discuss the varied roles of Notch in cancer, focusing on cell autonomous activities that may be either oncogenic or tumor suppressive.
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                Author and article information

                Journal
                Biol Open
                Biol Open
                BIO
                biolopen
                Biology Open
                The Company of Biologists Ltd
                2046-6390
                15 February 2018
                1 February 2018
                1 February 2018
                : 7
                : 2
                : bio029637
                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
                Author notes
                [*]

                These authors contributed equally to this work

                []Author for correspondence ( wanzhongge@ 123456zju.edu.cn )
                Author information
                http://orcid.org/0000-0003-1036-4134
                http://orcid.org/0000-0001-5056-7708
                http://orcid.org/0000-0003-1334-2723
                Article
                BIO029637
                10.1242/bio.029637
                5861358
                29437043
                2cf43198-185d-4046-96a5-f3a814e3d344
                © 2018. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 6 November 2017
                : 22 January 2018
                Funding
                Funded by: National Natural Science Foundation of China, http://dx.doi.org/10.13039/501100001809;
                Award ID: 31371319
                Award ID: 31371381
                Funded by: Ministry of Education of the People's Republic of China, http://dx.doi.org/10.13039/501100002338;
                Funded by: Ministry of Science and Technology of the People's Republic of China, http://dx.doi.org/10.13039/501100002855;
                Award ID: 2013CB945600
                Categories
                Research Article

                Life sciences
                notch,hdac1,atrophin,drosophila wing development
                Life sciences
                notch, hdac1, atrophin, drosophila wing development

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