Fleischer S, Wiemann S, Will H, Hofmann TG

Heinrich-Pette-Institut fuer Experimentelle Virologie und Immunologie, Martinistrasse 52, 20251 Hamburg, Germany.

Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional regulation. Here we identify a novel transcriptional repressor, PML-associated repressor of transcription (PAROT), which is regulated in its repressor activity through recruitment to PML-NBs. PAROT is a Krueppel-associated box ( KRAB) zinc-finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a linker domain and 8 tandemly repeated C(2)H(2)-ZNF motifs at its carboxy terminus. Consistent with its domain structure, when tethered to DNA, PAROT represses transcription, and this is partially released by the HDAC inhibitor trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1 (HP1) family and with transcriptional intermediary factor-1beta/KRAB-associated protein 1 (TIF-1beta/KAP1), a transcriptional corepressor for the KRAB-ZNF family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently recruits PAROT and TIF-1beta from heterochromatin to PML-NBs. PML-NB recruitment of PAROT partially releases its transcriptional repressor activity, indicating that PAROT can be regulated through subnuclear compartmentalization. Taken together, our data identify a novel transcriptional repressor and provide evidence for its regulation through association with PML-NBs.

Mesh Terms:
Amino Acid Sequence, Cell Line, Cell Nucleus, Cells, Cultured, Cloning, Molecular, Gene Expression Profiling, Humans, Kruppel-Like Transcription Factors, Molecular Sequence Data, Mutation, Neoplasm Proteins, Nuclear Proteins, RNA, Messenger, Repressor Proteins, Transcription Factors, Tumor Suppressor Proteins

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