HETEROCHROMATIN EFFECTS ON THE FREQUENCY AND DURATION OF LCR-MEDIATEDGENE-TRANSCRIPTION

Locus control regions (LCRs) are responsible for initiating and mainta ining a stable tissue-specific open chromatin structure of a locus. In transgenic mice, LCRs confer high level expression on linked genes in dependent of position in the mouse genome. Here we show that an incomp lete LCR loses this property when integrated into heterochromatic regi ons. Two disruption mechanisms were observed. One is classical positio n-effect variegation, resulting in continuous transcription in a clona l subpopulation of cells. The other is a novel mechanism resulting in intermittent gene transcription in all cells. We conclude that only a complete LCR fully overcomes heterochromatin silencing and that it con trols the level of transcription by ensuring activity in all cells at all times rather than directly controlling the rate of transcription.