Heterochromatin protein 1 (HP1a) has conserved roles in gene silencing and 
heterochromatin and is also implicated in transcription, DNA replication, and 
repair. Here we identify chromatin-associated protein and RNA interactions of 
HP1a by BioTAP-XL mass spectrometry and sequencing from Drosophila S2 cells, 
embryos, larvae, and adults. Our results reveal an extensive list of known and 
novel HP1a-interacting proteins, of which we selected three for validation. A 
strong novel interactor, dADD1 (Drosophila ADD1) (CG8290), is highly enriched in 
heterochromatin, harbors an ADD domain similar to human ATRX, displays selective 
binding to H3K9me2 and H3K9me3, and is a classic genetic suppressor of 
position-effect variegation. Unexpectedly, a second hit, HIPP1 (HP1 and 
insulator partner protein-1) (CG3680), is strongly connected to CP190-related 
complexes localized at putative insulator sequences throughout the genome in 
addition to its colocalization with HP1a in heterochromatin. A third interactor, 
the histone methyltransferase MES-4, is also enriched in heterochromatin. In 
addition to these protein-protein interactions, we found that HP1a selectively 
associated with a broad set of RNAs transcribed from repetitive regions. We 
propose that this rich network of previously undiscovered interactions will 
define how HP1a complexes perform their diverse functions in cells and 
developing organisms.