Figure 8. Model: Mechanism of repression.

A) A Bhlhb5 homodimer binds to its consensus binding element (1) and then recruits Prdm8 to mediate repression (2). Bhlhb5 requires Prdm8 to mediate repression, whereas Prdm8 requires Bhlhb5 for proper targeting to Bhlhb5 target genes. B) A schematic illustrating phylogenetic relationships among murine Bhlhb5-related proteins and Prdm8-related proteins, including Zfp488, a zinc finger protein that shows a very high degree of similarity with Prdm8 over the C-terminus (including the C₂H₂ zinc fingers) but lacks the SET domain characteristic of other Prdm family members. Our study reveals that Bhlhb5 and Prdm8 are obligate partners and others have shown that Olig2 interacts physically and functionally with Zfp488 (Wang et al., 2006), suggesting that the interaction between bHLH transcription factors and Prdm-related proteins may be a general mechanism of repression during neuronal development. Note that branch lengths are not scaled to distances. C) Prdm8 and Zfp488 show a very high degree of similarity across their C-termini. Amino acids 609 – 687 (for murine Prdm8) and 258 – 337 (for murine Zfp488) are shown. Identity = 53/80 (66%); Positives = 66/80 (82%); Gaps = 1/80 (1%). E-value, 3-e28. NLS, nuclear localization sequence.