Biology of Polycomb and Trithorax Group Proteins Achim Breiling, Luca Sessa, and Valerio Orlando Dulbecco Telethon Institute, Institute of Genetics and Biophysics, CNR, 80131 Naples, Italy Cellular phenotypes can be ascribed to different patterns of gene expression. Epigenetic mechanisms control the generation of different phenotypes from the same genotype. Thus differentiation is basically a process driven by changes in gene activity during development, often in response to transient factors or environmental stimuli. To keep the specific characteristics of cell types, tissue‐specific gene expression patterns must be transmitted stably from one cell to the daughter cells, also in the absence of the early‐acting determination factors. This heritability of patterns of active and inactive genes is enabled by epigenetic mechanisms that create a layer of information on top of the DNA sequence that ensures mitotic and sometimes also meiotic transmission of expression patterns. The proteins of the Polycomb and Trithorax group comprise such a cellular memory mechanism that preserves gene expression patterns through many rounds of cell division. This review provides an overview of the genetics and molecular biology of these maintenance proteins, concentrating mainly on mechanisms of Polycomb group‐mediated repression. KEY WORDS: Epigenetics, Epigenome, Polycomb, Repression, Polycomb group response elements, Maintenance proteins, Maintenance elements, Epigenetic marks. ß 2007 Elsevier Inc. I. Introduction In the early 1940s, Eleanor H. Slifer isolated a mutation in Drosophila melanogaster that showed a particular phenotype: male extra sex combs (Slifer, 1942). This phenotype turned out to be characteristic for mutations International Review of Cytology, Vol. 258 83 0074-7696/07 $35.00 Copyright 2007, Elsevier Inc. All rights reserved. DOI: 10.1016/S0074-7696(07)58002-2