RRC ID 32499
著者 Komori H, Xiao Q, Janssens DH, Dou Y, Lee CY.
タイトル Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor buttonhead.
ジャーナル Elife
Abstract The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. In this study, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.
巻・号 3
公開日 2014-10-6
DOI 10.7554/eLife.03502
PMID 25285447
PMC PMC4221733
MeSH Animals Brain / cytology Brain / growth & development Brain / metabolism* Cell Differentiation Cell Lineage / genetics Cell Nucleus / genetics Cell Nucleus / metabolism Chromatin / chemistry Chromatin / metabolism Chromosomal Proteins, Non-Histone / genetics* Chromosomal Proteins, Non-Histone / metabolism DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Epigenesis, Genetic Gene Expression Regulation, Developmental* Genetic Loci Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Larva / cytology Larva / genetics Larva / growth & development Larva / metabolism Mutation Myeloid-Lymphoid Leukemia Protein / genetics Myeloid-Lymphoid Leukemia Protein / metabolism Neural Stem Cells / cytology Neural Stem Cells / metabolism* Transcription Factors / genetics* Transcription Factors / metabolism Transcription, Genetic
IF 7.08
引用数 9
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