Biology Reference
In-Depth Information
initiate mRNA synthesis), chromatin must be uncoiled, a process which occurs
in at least three stages: the unfolding of large chromosomal domains (25-100 kb),
the remodeling of the chromatin structure of gene regulatory regions and the
alteration of nucleosome structure in transcribed regions (Jackson, 1997).
Unfolding reveals binding sites on the chromosomal DNA for activator proteins.
Once bound, these proteins alter nucleosome positioning and reveal further
binding sites for activator proteins. Decondensed chromatin thus provides an
accessible template for the assembly of the transcriptional initiation complex.
Centromeres.
The centromere is essential for normal disjunction of the chromo-
somes following cellular division at meiosis and mitosis. Centromeric DNA con-
sists of arrays of tandemly repeated DNA sequences which have undergone
homogenization by repeated genetic exchanges (Lee
et al
., 1997; Warburton
et al
.,
1993). Alphoid satellite DNA is the only satellite DNA family known to be pre-
sent in the centromeric regions of all human chromosomes. The basic 169 and 172
bp repeats of this primate-specific satellite DNA comprise the bulk of human cen-
tromeric DNA and contain a 17 bp binding site for the centromere-specific pro-
tein CENP-B. This binding site motif is present at the centromeres in the
chromosomes of all the anthropoid apes but is absent from the genomes of Old
and New World monkeys and prosimians (Haaf
et al
., 1995). It is also absent from
human Y chromosomal alphoid satellite DNA (Jørgensen, 1997).
Human alphoid satellite DNA may be divided into subsets which are largely
chromosome-specific (Jørgensen, 1997). They may however be grouped into
four supra-chromosomal families each characterized by a specific monomer
type (Jørgensen, 1997). Homologies exist between alphoid satellite DNAs from
different ape species but these are not associated with homologous chromo-
somes (Samonte
et al
., 1997; Warburton
et al
., 1996). Although alphoid satellite
repeats may have evolved from a common ancestral repeat monomer (Haaf and
Willard, 1998), they have also been subject to concerted evolution between
homologous chromosomes within a given species (Haaf and Willard, 1997;
Jørgensen
et al
., 1992).
Using a combination of oligonucleotide primer extension and immunocyto-
chemistry, Mitchell
et al
. (1992) showed that the alphoid repeats were closely asso-
ciated with the
kinetochore
(the structural element on the chromosome that binds
to the mitotic spindle). The presence of (AATGG)n (CCATT)n repeats in the cen-
tromeric region suggests that stem-loop structures might form which could serve
as specific recognition sites for kinetochore function (Catasti
et al
., 1994). Alphoid
satellite DNA sequences are not however restricted to centromeric regions
(Baldini
et al
., 1993).
Telomeres.
Telomeres allow the end of the chromosomal DNA to be replicated
completely without the loss of bases at the termini (reviewed by Blackburn, 1994;
Gilson
et al
., 1993). They are the sites at which the pairing of homologous chro-
mosomes is initiated and in humans contain long arrays (averaging about 10-15
kb) of minisatellite DNA comprising tandem hexanucleotide repeats, most fre-
quently TTAGGG (Brown, 1989). Other telomeric hexanucleotide repeats (e.g.
TTGGGG, TGAGGG) are also known (Allshire
et al
., 1989; Brown, 1989). These