title: Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1.
abstract: Latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) mediates the episomal replication of the KSHV genome, as well as transcriptional regulation, in latently infected cells. Interaction of LANA-1 with cellular chromatin is required for both these functions. An N-terminal heterochromatin-binding site in LANA-1 is essential for the replication and maintenance of latent episomes, as well as transcriptional regulation. We have recently described a C-terminal domain in LANA-1 that modulates the interaction with cellular interphase chromatin or elements of the nuclear matrix. Here, we used a series of LANA-1 deletion mutants to investigate the relationship between the different functions of LANA-1 and its interaction with the host chromatin-binding protein Brd2/RING3. Our findings suggest that the C-terminal chromatin-binding domain in LANA-1 is required for multiple LANA-1 functions, including the ability to bind to and replicate viral episomal DNA, to modulate transcription, and to interact with Brd2/RING3. Similar to the recently described tethering of bovine papillomavirus E2 protein to host chromatin via Brd4/MCAP, Brd2/RING3, another member of the Brd family of chromatin-binding proteins, therefore interacts with a chromatin-binding region of another viral latent nuclear protein and could play a role in its multiple functions.
authors.affiliation: Department of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Abel
authors.initials: A
authors.lastname: Viejo-Borbolla
authors.forename: Matthias
authors.initials: M
authors.lastname: Ottinger
authors.forename: Eva
authors.initials: E
authors.lastname: Brüning
authors.forename: Antje
authors.initials: A
authors.lastname: Bürger
authors.forename: Regina
authors.initials: R
authors.lastname: König
authors.forename: Emrah
authors.initials: E
authors.lastname: Kati
authors.forename: Julie A
authors.initials: JA
authors.lastname: Sheldon
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schulz
mesh_terms: D000956:Antigens, Viral / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D006566:Herpesviridae Infections / Q000821:virology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012514:Sarcoma, Kaposi / Q000821:virology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014779:Virus Replication; D000092468:Bromodomain Containing Proteins
chemical_list: D000956:Antigens, Viral; D002843:Chromatin; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins; C109540:latency-associated nuclear antigen