The dynamics of globin gene expression and gene therapy vectors.
The most important level of the regulation of the beta-globin genes is by activation of all of the genes by the locus control region (LCR). Part of the developmental regulation of the locus is achieved by competition of the genes for the interaction with the LCR. Although this level of gene regulation is quantitatively of less importance than the direct repression mechanism for the early genes, it has important implications and has provided an excellent assay to probe the regulation of transcription at the single cell level. The results of these studies indicate that the LCR interacts with individual globin genes and that LCR/gene interactions are dynamic with complexes forming and dissociating continually. We conclude that transcription only appears to take place while the LCR and gene interact and that the level of transcription is determined by the frequency and duration of such interaction rather than by changes in the rate of transcription of the promoters. This mechanism has clear implications for the design of vectors for the purpose of gene therapy.
Grosveld
F
F
MGC-Department of Cell Biology and Genetics, Erasmus University, The Netherlands.
de Boer
E
E
Dillon
N
N
Fraser
P
P
Gribnau
J
J
Milot
E
E
Trimborn
T
T
Wijgerde
M
M
D000818:Animals; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region; D014158:Transcription, Genetic
D005914:Globins