The formation of a highly condensed chromosome structure (heterochromatin) in a region of a eukaryotic chromosome can inactivate the genes within that region. Genetic studies using the fruitfly Drosophila melanogaster have identified several essential genes which influence the formation of heterochromatin. My purpose in this review is to summarize some recent work on the genetics of heterochromatin assembly in Drosophila and a recent model for how chromosomal proteins may interact to form a heterochromatic structure.

Eukaryotes organize certain chromosomal intervals into domains capable of si lencing most genes. Examples of silencing domains include the HML/HMR loci and subtelomeric chromatin in yeast, the Barr body X chromosome in mammals, and the pericentric heterochromatin of Drosophila. Silencing chromatin is often correlated with more regularized nucleosomal array than that found in active chromatin, and transcriptional activators appear to be missing from their target sites in silent chromatin. In Drosophila, gene silencing by heterochromatin is often variegated, indicating that a (...) gene may escape silencing in some cells. In a recent study, Ahmad and Henikoff(1) show that a yeast activator can compete successfully with Drosophila heterochromatic silencing factors for target sites in DNA. This competition, together with developmental change in the stability of heterochromatin itself, decides the transcriptional state for a gene subject to heterochromatin repression. BioEssays 23:767–771, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Most tissues contain cells capable of the self‐renewal and differentiation necessary to maintain tissue and organ integrity. These somatic stem cells are generally thought to have limited developmental potential. The mechanisms that restrict cell fate decisions in somatic stem cells are only now being understood. This understanding will be important in the clinical exploitation of adult stem cells in tissue repair and replacement. Experiments performed over fifty years ago in Drosophila showed that developmental restriction could be relaxed in the proliferating (...) larval cells that are destined to form the adult fly integument. This phenomenon, called transdetermination, can serve as a model for mechanisms of stem‐cell commitment. A recent publication1 sheds new light on the mechanism of transdetermination by demonstrating that loss of homeotic gene silencing leads to increased frequency of transdetermination. In addition, the authors link a specific signaling pathway induced by tissue regeneration to the relaxation of homeotic gene silencing. The data identify key mechanisms that control developmental homeostasis and cell fate restriction that could be manipulated to make somatic stem‐cell engineering possible. BioEssays 28: 574–577, 2006. © 2006 Wiley Periodicals, Inc. (shrink)