title: Drosophila RB proteins repress differentiation-specific genes via two different mechanisms.
abstract: The RB and E2F proteins play important roles in the regulation of cell division, cell death, and development by controlling the expression of genes involved in these processes. The mechanisms of repression by the retinoblastoma protein (pRB) have been extensively studied at cell cycle-regulated promoters. However, little is known about developmentally regulated E2F/RB genes. Here, we have taken advantage of the simplicity of the E2F/RB pathway in flies to inspect the regulation of differentiation-specific target genes. These genes are repressed by dE2F2/RBF and a recently identified RB-containing complex, dREAM/MMB, in a cell type- and cell cycle-independent manner. Our studies indicate that the mechanism of repression differs from that of cell cycle-regulated genes. We find that two different activities are involved in their regulation and that in proliferating cells, both are required to maintain repression. First, dE2F2/RBF and dREAM/MMB employ histone deacetylase (HDAC) activities at promoter regions. Remarkably, we have also uncovered an unconventional mechanism of repression by the Polycomb group (PcG) protein Enhancer of zeste [E(Z)], which is involved in silencing of these genes through the dimethylation of histone H3 Lys27 at nucleosomes located downstream of the transcription start sites (TSS).
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Hangnoh
authors.initials: H
authors.lastname: Lee
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Ohno
authors.forename: Yekaterina
authors.initials: Y
authors.lastname: Voskoboynik
authors.forename: Linda
authors.initials: L
authors.lastname: Ragusano
authors.forename: Anna
authors.initials: A
authors.lastname: Martinez
authors.forename: Dessislava K
authors.initials: DK
authors.lastname: Dimova
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D006657:Histones; C410303:RB protein, Drosophila; D006655:Histone Deacetylases