title: The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages.
abstract: The control of self-renewal and differentiation of neural stem and progenitor cells is a crucial issue in stem cell and cancer biology. Drosophila type II neuroblast lineages are prone to developing impaired neuroblast homeostasis if the limited self-renewing potential of intermediate neural progenitors (INPs) is unrestrained. Here, we demonstrate that Drosophila SWI/SNF chromatin remodeling Brahma (Brm) complex functions cooperatively with another chromatin remodeling factor, Histone deacetylase 3 (HDAC3) to suppress the formation of ectopic type II neuroblasts. We show that multiple components of the Brm complex and HDAC3 physically associate with Earmuff (Erm), a type II-specific transcription factor that prevents dedifferentiation of INPs into neuroblasts. Consistently, the predicted Erm-binding motif is present in most of known binding loci of Brm. Furthermore, brm and hdac3 genetically interact with erm to prevent type II neuroblast overgrowth. Thus, the Brm-HDAC3-Erm repressor complex suppresses dedifferentiation of INPs back into type II neuroblasts. DOI: http://dx.doi.org/10.7554/eLife.01906.001.
authors.affiliation: Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School Singapore, Singapore, Singapore.
authors.forename: Chwee Tat
authors.initials: CT
authors.lastname: Koe
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Rossi
authors.forename: Jack Jing Lin
authors.initials: JJ
authors.lastname: Wong
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhizhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Keng
authors.initials: K
authors.lastname: Chen
authors.forename: Sherry Shiying
authors.initials: SS
authors.lastname: Aw
authors.forename: Helena E
authors.initials: HE
authors.lastname: Richardson
authors.forename: Paul
authors.initials: P
authors.lastname: Robson
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
authors.forename: Cayetano
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation; D002460:Cell Line; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D058953:Neural Stem Cells / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D015534:Trans-Activators; D014157:Transcription Factors; C086469:brm protein, Drosophila; C547809:erm protein, Drosophila; C582193:Hdac3 protein, Drosophila; D006655:Histone Deacetylases
keywords: Drosophila; dedifferentiation; differentiation; intermediate neural progenitor; neuroblast; self-renewal