Heterochromatin: stable and unstable invasions at home and abroad (original) (raw)

  1. Jill A. Fahrner and
  2. Stephen B. Baylin1
  3. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-1000, USA; The Graduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA

One of the most vibrant areas of biology at present concerns elucidation of the “epigenetic” molecular mechanisms underlying how genomes are packaged to facilitate heritable gene expression patterns. An explosion of recent findings reveals how various components of chromatin regulate this process. Especially exciting is the dynamic role played by histone posttranslational modifications, which some have termed the “histone code” (Strahl and Allis 2000; Jenuwein and Allis 2001; Kouzarides 2002). Equally important are the proteins that read this code and interpret the signals to modulate transcriptional potential (Eissenberg and Elgin 2000; Lachner et al. 2001). Much of what we have learned about these molecular parameters has come from the study of large regions of DNA packaged into, and heritably transmitted as, permanently transcriptionally silenced regions termed constitutive heterochromatin (Wakimoto 1998; Grewal and Elgin 2002). In classic studies with Drosophila, molecular determinants have been elucidated to explain variegated patterns of heritable gene expression, or position effect variegation (PEV), which emerge when a gene that normally resides in active euchromatin is translocated into such heterochromatin (Wallrath and Elgin 1995; Wakimoto 1998; Grewal and Elgin 2002). In this issue of Genes & Development, a clever experimental system initially designed to explore the role of heterochromatin in the silencing of specific genes unexpectedly reveals that the opposite situation, invasion of heterochromatin into a euchromatic region, also triggers a variegated pattern of heritable gene silencing (Ayyanathan et al. 2003). These findings have important ramifications for gene expression in settings of both normal and pathological cellular function.

Sharing the players to form different types of heterochromatin

The paper by Ayyanathan et al. (2003) is highly relevant to rapidly changing concepts about whether heterochromatin always occupies exclusive domains of the genome distinct from euchromatin. If so, this would logically suggest that the players and mechanisms involved in forming …