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The Dynamics of Globin Gene Expression and Gene Therapy Vectors
Author(s) -
GROSVELD FRANK,
BOER ERNIE,
DILLON NIALL,
GRIBNAU JOOST,
MILOT ERIC,
TRIMBORN TOLLEIV,
WIJGERDE MARK,
FRASERA PETER
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10458.x
Subject(s) - gene , locus control region , promoter , biology , transcription (linguistics) , psychological repression , genetics , gene expression , regulation of gene expression , globin , locus (genetics) , transcription factor , linguistics , philosophy
A bstract : The most important level of regulation of the β‐globin genes is by activation of all of the genes by the Locus Control Region (LCR) and repression of the early genes by an as yet unknown factor acting on sequences flanking the genes. Superimposed on this is a mechanism in which the early genes (ɛ and γ) suppress the late genes (δ and β) by competition for the interaction with the LCR. Although this extra level of gene regulation is quantitatively of less importance than the direct repression mechanism, it has important implications and has provided an excellent assay system to probe the regulation of transcription at the single cell level. These studies indicate that the LCR interacts with individual globin genes and that LCR/gene interactions are dynamic with complexes forming and dissociating continually. The levels of expression of each of the genes appear to depend on: 1) the frequency of interaction which is itself dependednt on the distance of the gene to the LCR, 2) the affinity of the LCR for the gene and 3) the stability of the LCR/gene complex. The latter two are dependent on the balance of transcription factors. 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 promoters.