B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity.

BAL1 (B-aggressive lymphoma 1) was originally identified as a risk-related gene in diffuse large B-cell lymphoma. BAL1 encodes a nuclear protein with N-terminal macro domains and a putative C-terminal poly(ADP-ribose) polymerase active site. Macro domains are sequences homologous to the non-histone region of histone macroH2A. Several lines of evidence suggest that these domains may modulate transcription, including a high concentration of histone macroH2A in the inactive X chromosome, direct interference with transcription factor binding in a positioned nucleosome, and structural similarity to DNA binding domains. Poly(ADP-ribosyl)ation is a critical post-translational modification that regulates chromatin configuration and transcription. In this report we describe two additional BAL family members, BAL2 and BAL3, with N-terminal macro domains and putative C-terminal active sites and assess the function of these specific regions in BAL family members. Herein, we demonstrate that BAL macro domains repress transcription when tethered to a promoter. In addition, we show that BAL2 and BAL3, but not BAL1, exhibit Pduanyu37 activity. In agreement with these data, BAL1 lacks several critical donor and acceptor residues that are conserved in the BAL2 and -3 Pduanyu37 active sites. Of interest, BAL family members with inactive or functional Pduanyu37 domains differed in their ability to repress transcription. BAL family members are the only described proteins with both Pduanyu37 and macro domains, underscoring the potential functional significance of this unique combination.

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