The beta-like globin gene cluster

Because of the existence of duplicated genes in this region, blind use of PIP is not recommended. However, the same tools can be applied in a customized manner to produce a similar kind of output. The plot shows some matches in the 5' and 3' flanks of the beta gene, and matches extending for over 16 kb upstream of the epsilon gene, in what is called the Locus Control Region. On the other hand, by first "zooming in" to the region before the epsilon gene (using the laj interface), one can get PIP output corresponding roughly to the first 20 kb of this plot.

Inspection of the plot suggests several hypotheses

• regulatory signals are spred throughout the LCR, not just at the HSs.
• there is a concentration of regulatory signals in the HS2 core.
• regulation of epsilon is more complicated than that of gamma (but note that mice regulate gamma different than humans do)
• there are regulatory elements in the 3' flank of beta of comparable "strength" to those in the 5' flank

References:

• R. Hardison and W. Miller (1993) Use of long sequence alignments to study the evolution and regulation of mammalian globin gene clusters. Molecular Biology and Evolution 10, 73-102.