We have used a kinetic analysis to distinguish possible mechanisms of
activation of transcription of the different genes in the human beta g
lobin locus. Based on in situ studies at the single-cell level we have
previously suggested a dynamic mechanism of single genes alternately
interacting with the locus control region (LCR) to activate transcript
ion. However, those steady-state experiments did not allow a direct me
asurement of the dynamics of the mechanism and the presence of loci wi
th in situ primary transcript signals from two beta-like genes in cis
has left open the possibility that multiple genes in the locus could i
nitiate transcription simultaneously. Kinetic assays involving removal
of a block to transcription elongation in conjunction with RNA FISH s
how that multiple beta gene primary transcript signals in cis represen
t a transition between alternating transcriptional periods of single g
enes, supporting a dynamic interaction mechanism.