During Drosophila development, the Polyeomb and trithorax group genes (Pc-G and trx-G) are required to maintain stable expression patterns for the clustered homeotlc genes fflOM. C) 1, 2. Several lines o! evidence suggest that PeG and trx-G exert their effects through interaction wlth, or modification of, chromatln. The Polycomb protein has a domain (terh,~ d the chromodomaln) also found in a heterochromatln~. blndlng protein, HPI (Ref. 3). Brahma, encoded by a trx-G gene, has extensive similarity (including a bromodomaln 4) to SWI21SNF2 (Ref. 5), which Is part of a multl-component transcriptional activator In yeast that appears to modulate the chromatln structure of the genes it regulates. Genetic analysis has also suggested that repression by Pc-G of successive regulatory regions of HOM~ occurs by a mechanism Involving propagation of a heterochromatlnqlke structure along the gene cluster a, 6The carboxy-termlnal part o| the trx protein shows shnllarity to the carboxyl terminus of the Enhancer of zeste protein, E (z), another member el the Pc. G, suggesting that there is a functional relationship among the Pc-G and trx43 genes 7. This relationship Is underscored by the fact that trx-G genes are Isolated as suppressors of Pc-G mutants. This type of chromatin-medlated transcriptional regulation appears to be conserved through evolution, since several vertebrate homologues of Pc-G and trx-G have been isolated. One example Is HRX (A/I. 1, M/I), a human homologue of trx involved In chromosomal translocatlons in acute leukaemla 8, 9.

Using the recently published sequence of the Pc. G protein Polycomblike (Pcl) l as a probe in sequence similarity searches, we found that a zinc-linger-like motif occurs twice in Pcl and t~ iree times tn trx and HRX (Fig. 1). This motif has a unique Cys4-His-Cys 3 pattern, spanning approximately 50-80 residues. The pattern of conservation, which includes additional conserved positions, is clearly distinct from two similarly sized motifs that also occur in nuclear regulatory proteins; the Cys.~-His-Cys4 RING linger n and the Cys2-HisLCys s LIM'domainl2, 13 (see Table I).