Tariq Enver

Developmental regulation of fetal to adult globin gene switching in human fetal erythroid × mouse erythroleukemia cell hybrids☆

Human fetal erythroid x murine erythroleukemia cell hybrids undergo human fetal (gamma) to adult (beta) globin gene switching in vitro under the control of a mechanism located on human chromosome 11. We investigated whether this mechanism acts in cis or in trans by preparing hybrid cells containing marked fragments of the gamma and beta genes known to switch in transgenic mice. In these cells the chromosomally introduced human globin locus undergoes the fetal to adult globin gene switch. In contrast, the marked globin gene fragments were expressed at all stages of hybrid development. These results suggest that either the mechanism of switching acts in cis or that sequences present in the chromosomal globin locus but missing from the transfected globin gene fragments mediate its action.

Primary structure of the goat β-globin locus control region

Abstract The goat β-globin cluster is composed of a triplicated four-gene set. A locus control region (LCR) containing elements homologous to 5′ DNase I hypersensitive sites (HS) 1, 2, and 3 of the human β-globin LCR has been identified at the 5′ end of this locus. We determined 10.2 kb of nucleotide sequence from the goat β-globin locus control region. Self-comparison of this sequence by dot matrix analysis revealed the presence of six complete and three incomplete artiodactyl repeats. A novel repeated element, termed D repeat, was also identified. Southern blotting analysis demonstrated that these elements exist in the goat genome as a low to medium frequency interspersed repeat family. The absence of any other large region of self-homology (direct or inverted) in the goat LCR suggests that 5′ HSs 1, 2, and 3 did not arise through duplication, but rather evolved independently. By comparing goat 5′ HS 1 to those of human, rabbit, and mouse, we show a greater than 80% conservation in sequence between the four species. This level of evolutionary conservation suggests that 5′ HS 1 plays an important role in the regulation of β-globin loci.