The Chromosomal High-Affinity Binding Sites for the Drosophila Dosage Compensation Complex

Dosage compensation in male Drosophila relies on the X
chromosome-specific recruitment of a chromatin-modifying machinery,
the dosage compensation complex (DCC). The principles that assure
selective targeting of the DCC are unknown. According to a
prevalent model, X chromosome targeting is initiated by recruitment
of the DCC core components, MSL1 and MSL2, to a limited number of
so-called ``high-affinity sites'' ( HAS). Only very few such sites
are known at the DNA sequence level, which has precluded the
definition of DCC targeting principles. Combining RNA interference
against DCC subunits, limited crosslinking, and chromatin
immunoprecipitation coupled to probing high-resolution DNA
microarrays, we identified a set of 131 HAS for MSL1 and MSL2 and
confirmed their properties by various means. The HAS sites are
distributed all over the X chromosome and are functionally
important, since the extent of dosage compensation of a given gene
and its proximity to a HAS are positively correlated. The sites are
mainly located on noncoding parts of genes and predominantly map to
regions that are devoid of nucleosomes. In contrast, the bulk of
DCC binding is in coding regions and is marked by histone H3K36
methylation. Within the HAS, repetitive DNA sequences mainly based
on GA and CA dinucleotides are enriched. Interestingly, DCC
subcomplexes bind a small number of autosomal locations with
similar features.