The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages

Elife. 2014 Mar 11;3:e01906. doi: 10.7554/eLife.01906.

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.

Keywords: Drosophila; dedifferentiation; differentiation; intermediate neural progenitor; neuroblast; self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Binding Sites
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Dedifferentiation*
  • Cell Line
  • Cell Lineage*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Multiprotein Complexes
  • Neural Stem Cells / metabolism*
  • Protein Binding
  • RNA Interference
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Multiprotein Complexes
  • Trans-Activators
  • Transcription Factors
  • brm protein, Drosophila
  • erm protein, Drosophila
  • Hdac3 protein, Drosophila
  • Histone Deacetylases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.