Human MED26 was originally purified in the cofactor required for the Sp1 
activation complex (CRSP) as a 70-kDa component named CRSP70. This polypeptide 
was specific to metazoans and the “small” form of the Mediator complex. We 
report here that a Drosophila melanogaster homologue of MED26 similarly 
interacts with other components of the core Drosophila Mediator complex but not 
with the kinase module and is recruited to genes upon activation. Using a null 
allele of Med26, we show that Med26 is required for organismal viability but not 
for cell proliferation or survival. Clones lacking Med26 in the wing disc lead 
to loss of the adult wing margin and reduced expression of genes involved in 
wing margin formation. Surprisingly, when polytene chromosomes from the salivary 
gland were examined using antibodies to Med26, it was apparent that a fraction 
of the protein was associated with the chromocenter, which contains pericentric 
heterochromatin. This staining colocalizes with heterochromatin protein 1 (HP1). 
Immunoprecipitation experiments show that Med26 interacts with HP1. The 
interaction is mediated through the chromoshadow domain of HP1 and through the 
conserved motif in the carboxy terminus of the Med26 protein. This work is the 
first characterization of the metazoan-specific Mediator subunit in an animal 
model.