Polycomb and Trithorax Group Genes in Drosophila

Abstract

Polycomb group (PcG) and Trithorax group (TrxG) genes encode important regulators of development and differentiation in metazoans. These two groups of genes were discovered in Drosophila by their opposing effects on homeotic gene (Hox) expression. PcG genes collectively behave as genetic repressors of Hox genes, while the TrxG genes are necessary for HOX gene expression or function. Biochemical studies showed that many PcG proteins are present in two protein complexes, Polycomb repressive complexes 1 and 2, which repress transcription via chromatin modifications. TrxG proteins activate transcription via a variety of mechanisms. Here we summarize the large body of genetic and biochemical experiments in Drosophila on these two important groups of genes.

Keywords: Drosophila; FlyBook; Polycomb; Trithorax.

Figure 1

Homeotic transformations are diagnostic phenotypes of PcG and TrxG mutants. (A) Shows the first tarsal segments of the first and second thoracic legs of adult males. The Hox gene Scr is expressed in the cells that form the first leg, causing the cells to differentiate the row of distinctive bristles called a sex comb. At the left of (A) is a wild-type male with a sex comb on the first leg. In the middle of (A) is a male with loss of Scr function and no sex comb on either first or second legs (a TrxG mutant phenotype). At the right of (A) is a male with ectopic expression Scr in the second leg and sex combs on both the first and second legs (a PcG phenotype). (B) Shows the wings and halteres of pharate adult flies. At the left is a wild-type fly and at the right is a homozygous trithorax^B27 mutant fly. Loss of function of the Hox gene Ubx in the third thoracic segment caused the differentiation of anterior wing structures in place of the haltere structures. There are also transformations of the posterior wing to a more anterior identity caused by en loss of function. (C) Shows the abdominal segments of adult males. At the left is a wild-type male and at the right is a grappa¹¹ mutant male. Loss of Abd-B function in the grappa mutant transformed the fifth abdominal segment to a fourth abdominal segment identity.

Figure 2

Developmental model of the regulation of Hox genes by the PcG and TrxG proteins. The establishment of the initial domain of the Hox gene Ubx by the segmentation proteins is shown at the top, with Ubx repressed anterior to its domain of expression by the Hb gap segmentation protein. The initial domain of Ubx expression is maintained through larval and pupal development by the TrxG proteins. Maintenance of silencing of the Ubx gene anterior to this domain requires both PcG proteins and trimethylation of lysine 27 on histone H3 (H3K27me3). Posterior to its normal domain of expression, Ubx is repressed by the Hox proteins Abd-A and Abd-B, not by the PcG proteins, or by histone H3K27me3.

Figure 3

PcG proteins and complexes. (A) PcG protein complexes discussed in this review are shown. Pcl, Jing, and Jarid2 are PRC2-associated proteins that modify the activity of PRC2 (see text). Psc/Su(z)2 and Sce (also known as dRing) are in both PRC1 and dRAF. A recent article provided compelling evidence that Scm interacts closely with PRC1, PRC2, and PhoRC, and suggested that Scm plays a key role in connecting these three complexes (Kang et al. 2015; see text). (B) PcG protein complexes are recruited to DNA by PREs. PREs have binding sites for a large number of DNA-binding proteins; Pho or Phol, Spps, GAF (encoded by the Trl gene), and Cg are shown. PRC2 trimethylates H3K27 and PRC1 inhibits transcription by a variety of mechanisms (see text). Me, methylation.

Figure 4

TrxG proteins and complexes that affect chromatin structure. (Top panel) TrxG proteins and protein complexes that modify histones. Complexes are shown, along with the histone modification(s) they catalyze. Proteins in green are designated TrxG proteins because mutants have TrxG phenotypes. All other subunits shown were identified as biochemical components of the complexes. (Bottom panel) TrxG proteins and protein complexes involved in chromatin remodeling. Proteins identified as products of genes whose mutants have TrxG phenotypes or that act as suppressors of Pc are in green. Pb, Bap170, and Sayp (blue) are present in PBAP, but not in BAP. All subunits shown in gray are present in both BAP and PBAP.