Format

Send to

Choose Destination
See comment in PubMed Commons below
Genes Dev. 2014 Jul 1;28(13):1445-60. doi: 10.1101/gad.241950.114.

Heterochromatin-associated interactions of Drosophila HP1a with dADD1, HIPP1, and repetitive RNAs.

Author information

1
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
2
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Institute of Molecular and Cellular Biology, Novosibirsk 630090, Russia;
3
Department of Biology, Tufts University, Medford, Massachusetts 02155, USA;
4
Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA; Hematology/Oncology Program, Children's Hospital, Boston, Massachusetts 02115, USA.

Abstract

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.

KEYWORDS:

Bayesian analysis; ChIP; HP1a; LC-MS/MS; formaldehyde cross-linking

PMID:
24990964
PMCID:
PMC4083088
DOI:
10.1101/gad.241950.114
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center