THE EFFECT OF DISTANCE ON LONG-RANGE CHROMATIN INTERACTIONS

We have used gene competition to distinguish between possible mechanis ms of transcriptional activation of the genes of the human beta-globin locus. The insertion of a second beta-globin gene at different points in the locus shows that the more proximal beta gene competes more eff ectively for activation by the locus control region (LCR). Reducing th e relative distance between the genes and the LCR reduces the competit ive advantage of the proximal gene, a result that supports activation by direct interaction between the LCR and the genes. Visualization of the primary transcripts shows that the level of transcription is propo rtional to the frequency of transcriptional periods and that such peri ods last approximately 8 min in vivo. We also find that the position o f the beta-globin gene in the locus is important for correct developme ntal regulation.