The Questions of Developmental Biology

In the embryos receiving the complete transgene
(which included the NSRE), expression was seen only
in the nervous system (Figure 5.17A). However, in those
mice whose transgene lacked the NRSE, expression was
seen in the heart, limb mesenchyme and limb ectoderm,
kidney mesoderm, ventral body wall, and cephalic mesenchyme
(Figure 5.17B).
Locus control regions in globin genes
There are some regions of DNA called locus control regions
(LCRs), which function as "super-enhancers." These LCRs establish an "open"
chromatin configuration, inhibiting the normal repression of transcription over an area spanning
several genes. The mechanism by which the LCR opens up the chromatin is not yet known.
One of the best-studied
LCRs is that regulating the
tissue-specific expression of the
β-globin family of genes in
humans, mice, and chicks. In
many species, including chicks
and humans, the embryonic or
fetal hemoglobin differs from
that found in adult red blood
cells (Figure 5.18).
Human hemoglobin consists
largely of four globin chains of
two different types and four
molecules of heme. Human embryonic hemoglobin has two zeta () globin chains and two
epsilon () globin chains (and four molecules of heme). During the second month of human
gestation, - and -globin synthesis abruptly ceases, while alpha () and gamma () globin
synthesis increases. The association of two -globin chains with two -globin chains
produces fetal hemoglobin ( 2 2 ). (The physiological importance of the -globin chain in fetal
hemoglobin is examined in Chapter 14.) At 3 months gestation, the beta (β) globin and delta ()
globin genes begin to be active, and their products slowly increase, while -globin levels
gradually decline. This switchover is greatly accelerated after birth, and fetal hemoglobin is
replaced by adult hemoglobin ( 2 β 2 ). The normal adult hemoglobin profile is 97% 2 β 2 , 2 3%
2 2 , and 1% 2 2 .
A schematic diagram of human hemoglobin types and the genes that code for them is
shown in Figure 5.19. In humans, the - and -globin genes are located on chromosome 16, but
the -, -, -, and β-globin genes (known as the β-globin gene family) are linked together, in
order of appearance, on chromosome 11. It appears, then, that there is a mechanism that directs
the sequential switching of the chromosome 11 genes from embryonic, to fetal, to adult globins.