title: Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling.
abstract: Chromatin remodeling processes are among the most important regulatory mechanisms in controlling cell proliferation and regeneration. Drosophila intestinal stem cells (ISCs) exhibit self-renewal potentials, maintain tissue homeostasis, and serve as an excellent model for studying cell growth and regeneration. In this study, we show that Brahma (Brm) chromatin-remodeling complex is required for ISC proliferation and damage-induced midgut regeneration in a lineage-specific manner. ISCs and enteroblasts exhibit high levels of Brm proteins; and without Brm, ISC proliferation and differentiation are impaired. Importantly, the Brm complex participates in ISC proliferation induced by the Scalloped-Yorkie transcriptional complex and that the Hippo (Hpo) signaling pathway directly restricted ISC proliferation by regulating Brm protein levels by inducing caspase-dependent cleavage of Brm. The cleavage resistant form of Brm protein promoted ISC proliferation. Our findings highlighted the importance of Hpo signaling in regulating epigenetic components such as Brm to control downstream transcription and hence ISC proliferation. DOI:http://dx.doi.org/10.7554/eLife.00999.001.
authors.affiliation: State Key Laboratory of Cell Biology , Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai , China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Jin
authors.forename: Jinjin
authors.initials: J
authors.lastname: Xu
authors.forename: Meng-Xin
authors.initials: MX
authors.lastname: Yin
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Lianxin
authors.initials: L
authors.lastname: Hu
authors.forename: Peixue
authors.initials: P
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Ho
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004789:Enzyme Activation; D007422:Intestines / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D000099317:Hippo Kinases
chemical_list: D020169:Caspases; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; C086469:brm protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: D. melanogaster; Hippo signaling; brahma; midgut