From flour to flower: how Polycomb group proteins influence multiple aspects of plant development

Cell identity and differentiation are determined by patterns of regulatory gene expression. Spatially and temporally regulated homeotic gene expression defines segment identities along the anterior-posterior axis of animal embryos. Polycomb group (PcG) proteins form a cellular memory system that maintains the repressed state of homeotic gene expression. Conserved PcG proteins control multiple aspects of Arabidopsis development and maintain homeotic gene repression. In animals, PcG proteins repress their target genes by modifying histone tails through deacetylation and methylation, generating a PcG-specific histone code that recruits other chromatin remodeling proteins to establish a stable, heritable mechanism of epigenetic expression control. Plant PcG proteins might function through a similar biochemical mechanism owing to their conserved structural and functional relationship to animal PcG proteins.     

Role of polycomb group proteins in stem cell self-renewal and cancer

Polycomb group proteins (PcG) form part of a gene regulatory mechanism that determines cell fate during normal and pathogenic development. The mechanism relies on epigenetic modifications on specific histone tails that are inherited through cell divisions, thus behaving de facto as a cellular memory. This cellular memory governs key events in organismal development as well as contributing to the control of normal cell growth and differentiation. Consequently, the dysregulation of PcG genes, such as Bmi1, Pc2, Cbx7, and EZH2 has been linked with the aberrant proliferation of cancer cells. Furthermore, at least three PcG genes, Bmi1, Rae28, and Mel18, appear to regulate self-renewal of specific stem cell types suggesting a link between the maintenance of cellular homeostasis and tumorigenesis. In this review, we will briefly summarize current views on PcG function and the evidence linking specific PcG proteins with the behavior of stem cells and cancer cells.     

Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway

Polycomb group (PcG) proteins play a role in the maintenance of cellular identity throughout many rounds of cell division through the regulation of gene expression. In this report we demonstrate that the loss of the PcG gene mel-18 impairs the expansion of the most immature T progenitor cells at a stage before the rearrangement of the TCR beta-chain gene in vivo and in vitro. This impairment of these T progenitors appears to be associated with increased susceptibility to cell death. We also show that the expression of Hes-1, one of the target genes of the Notch signaling pathway, is drastically down-regulated in early T progenitors isolated from mel-18(-/-) mice. In addition, mel-18(-/-) T precursors could not maintain the Hes-1 expression induced by Delta-like-1 in monolayer culture. Collectively, these data indicate that mel-18 contributes to the maintenance of the active state of the Hes-1 gene as a cellular memory system, thereby supporting the expansion of early T progenitors.     

Programming of gene expression by Polycomb group proteins

Polycomb group (PcG) complexes maintain epigenetically repressed states that need to be reprogrammed when cells become committed to differentiation. In contrast to the previously held belief that PcG complexes regulate only a few selected genes, recent efforts have revealed hundreds of potential PcG targets in mammals, insects and plants. These results have changed our perception about PcG recruitment and function on chromatin. Both in animals and plants, evolutionarily conserved PcG complexes mark the chromatin of their target genes by methylation at histone H3 lysine 27. Surprisingly, however, both the proteins recognizing this mark and the mechanisms causing gene repression differ between both kingdoms. This suggests that different developmental strategies used in plant and animal development entailed the evolution of different repressive maintenance mechanisms.     

dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations

To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG) proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle. In the absence of PcG, ectopic activation of the PcG-repressed genes leads to developmental defects and malignant tumors. Little is known about the molecular nature of ectopic gene expression; especially what differentiates expression of a given gene in the orthotopic tissue (orthotopic expression) and the ectopic expression of the same gene due to PcG mutations. Here we present that ectopic gene expression in PcG mutant cells specifically requires dBRWD3, a negative regulator of HIRA/Yemanuclein (YEM)-mediated histone variant H3.3 deposition. dBRWD3 mutations suppress both the ectopic gene expression and aberrant tissue overgrowth in PcG mutants through a YEM-dependent mechanism. Our findings identified dBRWD3 as a critical regulator that is uniquely required for ectopic gene expression and aberrant tissue overgrowth caused by PcG mutations.     

Diverse functions of Polycomb group proteins during plant development

Polycomb group (PcG) proteins play essential roles in animal and plant life cycles by controlling the expression of important developmental regulators. These structurally heterogeneous proteins form multimeric protein complexes that control higher order chromatin structure and, thereby, the expression state of their target genes. Once established, PcG proteins maintain silent gene expression states over many cell divisions providing a molecular basis for a cellular 'memory.' PcG proteins are best known for their role in the control of homeotic genes in Drosophila and mammals. In addition, they play important roles in the control of cell proliferation in vertebrate and invertebrate systems. Recent studies in plants have shown that PcG proteins regulate diverse developmental processes and, as in animals, they affect both homeotic gene expression and cell proliferation. Thus, the function of PcG proteins has been widely conserved between the plant and animal kingdoms.     

Division of labor in polycomb group repression

The epigenetic maintenance of gene expression patterns is essential for developing and maintaining the diverse types of cell that cooperate to form the larger organism. Recent data suggest that proteins of the Polycomb group (PcG) use a combination of posttranslational modifications and structural changes to the underlying chromatin structure to maintain silenced epigenetic states. We are now beginning to understand the mechanisms by which the PcG proteins are able to silence genes and to maintain this silencing over many cell divisions.     

Polycomb group and trithorax group proteins in Arabidopsis

Polycomb group (PcG) and trithorax group (trxG) proteins form molecular modules of a cellular memory mechanism that maintains gene expression states established by other regulators. In general, PcG proteins are responsible for maintaining a repressed expression state, whereas trxG proteins act in opposition to maintain an active expression state. This mechanism, first discovered in Drosophila and subsequently in mammals, has more recently been studied in plants. The characterization of several Polycomb Repressive Complex 2 (PRC2) components in Arabidopsis thaliana constituted a first breakthrough, revealing key roles of PcG proteins in the control of crucial plant developmental processes. Interestingly, the recent identification of plant homologues of the Drosophila trithorax protein suggests a conservation of both the PcG and trxG gene regulatory system in plants. Here, we review the current evidence for the role of PcG and trxG proteins in the control of plant development, their biochemical functions, their interplay in maintaining stable expression states of their target genes, and point out future directions which may help our understanding of PcG and trxG function in plants.