Cross-regulation among the polycomb group genes in Drosophila melanogaster

Abstract

Genes of the Polycomb group in Drosophila melanogaster function as long-term transcriptional repressors. A few members of the group encode proteins found in two evolutionarily conserved chromatin complexes, Polycomb repressive complex 1 (PRC1) and the ESC-E(Z) complex. The majority of the group, lacking clear biochemical functions, might be indirect regulators. The transcript levels of seven Polycomb group genes were assayed in embryos mutant for various other genes in the family. Three Polycomb group genes were identified as upstream positive regulators of the core components of PRC1. There is also negative feedback regulation of some PRC1 core components by other PRC1 genes. Finally, there is positive regulation of PRC1 components by the ESC-E(Z) complex. These multiple pathways of cross-regulation help to explain the large size of the Polycomb group family of genes, but they complicate the genetic analysis of any single member.

FIG. 1.

Psc is positively regulated by E(Pc), Pcl, and Asx. The graphs show the differences in mRNA levels between mutant and wild-type embryos, plotted on a log₂ scale. The RNA abundance levels for each preparation of embryonic RNA were normalized by comparison to mRNA levels of a ribosomal protein gene. Psc RNA levels are decreased in embryos mutant for E(Pc) (A), Pcl (B), and Asx (C). Pc and ph-d RNA levels also tended to fall below wild-type levels.

FIG. 2.

Psc and Su(z) 2 are negatively regulated by PRC1 core members Psc, Pc, and ph. Psc and Su(z) 2 RNA levels are increased in embryos mutant for Psc (A), Pc (B), and ph (C). Su(z) 2 RNA levels were similarly increased in an Scm mutant (D). Data are presented as in Fig. 1.

FIG. 3.

Pc is positively regulated by esc and E(z). Pc RNA levels are decreased in embryos mutant for esc (A) and E(z) (B). Psc and ph-d RNA levels are also reduced in esc mutant embryos. Data are presented as in Fig. 1.

FIG. 4.

Increases in Su(z) 2 RNA were not tissue specific. RNA in situ hybridizations show Su(z) 2 transcripts in germ band-retracted embryos. All embryos were stained for the same amount of time. The embryos were cut along the dorsal midline and were flattened to display all of the epidermis in one focal plane. (A) Wild-type embryo (w.t.); (B) Pc^XT109 homozygote (Pc); (C) ph⁵⁰³ homozygote (ph); (D) Psc^e24 homozygote (Psc).

FIG. 5.

Model for PcG interactions. PRC1 core members repress the homeotic genes, including the bithorax complex (BX-C). E(Pc), Pcl, and Asx act as upstream positive regulators of PRC1 core members. A second level of regulation is the negative feedback by PRC1 core members on Psc and RING1. There is also repression of Su(z) 2, whose downstream targets are unclear. A third level of regulation is that the ESC-E(Z) complex acts as a positive regulator of Pc transcription.