BMC Genomics 2008, 9:308 http://www.biomedcentral.com/1471-2164/9/308 [6], and in the vernalization response [7]. Hence, PcG pro- teins play an essential role in the proper development of multicellular organisms. Biochemical and genetic characterizations of PcG proteins have revealed that they exist in distinct multi-protein complexes [8,9], of which the two best characterized are the PcG repressive complex (PRC)1 and PRC2. The core components of PRC2 are conserved throughout higher eukaryotes. The complex mediates histone H3 methyla- tion at lysine 27 [10-12]. Similar complexes have been found in Caenorhabditis elegans [13,14], vertebrates [10- 12,15,16] and plants [4,5]. Unlike PRC2, PRC1-like complexes have only been described in Drosophila and vertebrates. Drosophila PRC1 core complex contains Posterior sex combs (Psc), Polyhomeotic (Ph), Drosophila Ring finger protein 1 or Sex combs extra (dRing1/Sce) and Polycomb (Pc) [17,18]. The complex can inhibit in vitro both chromatin remode- ling by the human SWItch/Sucrose NonFermentable (hSWI/SNF) complex [19,20] and transcription of a chro- matin template by RNA polymerase II [21]. The human PRC1 complex is composed of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), PH2, PC3, and the Ring finger proteins (Ring1A/RING1 and Ring1B/ RING2), homologs of Drosophila Psc, Ph, Pc, and dRing, respectively. Human Bmi1, Ring1A and Ring1B proteins form an E3 ubiquitin ligase complex that mono-ubiquiti- nates lysine 119 of nucleosomal histone H2A (H2A- K119) [22,23]. The H2A-K119 monoubiquitination is required for the PcG-mediated in vivo gene silencing, but its role in the mechanism is not yet known [23]. Dro- sophila PRC1 presumably possesses ubiquitin E3 ligase activity as well, since dRing was found to co-localize with ubiquitinated H2A at the Ultrabithorax (Ubx) promoter [22]. In Drosophila and vertebrates the PcG-mediated gene silencing mechanism requires the action of both PRC2 and PRC1. The apparent lack of homologs of PRC1 com- ponents in organisms such as plants or worms and the conflicting information on histone ubiquitination in these organisms led to the speculation of alternative PcG- mediated gene silencing mechanism in which other pro- teins undertake PRC1 functions [4,24-29]. Ubiquitination at lysine 119 of H2A in human was observed within the consensus peptide sequence PKKT [22]. Arabidopsis genome contains 13 histone H2A genes (HTA1-13) [30], among them just HTA10 displays conservation of the PKKT consensus sequence. Although H2A ubiquitination has not been detected in Arabidopsis using western blot analysis so far [31], a recent report showed the presence of ubiquitinated H2A in maize [32]. On the other hand, ubiquitinated H2A has been detected in C. elegans [29], indicating that some proteins may be involved in H2A ubiquitination. The catalytic subunit of the mammalian E3 ubiquitin ligase complex is Ring1B, but Ring1A and Bmi-1 are also required for the in vivo H2A ubiquitination [31]. Bmi-1, Ring1B and Ring1A contain a Ring finger domain located at the N-terminal region. Biochemical analyses showed that the N-terminal Ring finger domain of Ring1B is suffi- cient for the E3 ligase activity in vitro [22,33,34] and that Bmi-1 displays no detectable ubiquitin ligase activity but it greatly stimulates the E3-ligase activity of Ring1B. It was also described that in vitro Ring1A can replace Ring1B [34]; however, the in vivo function must be distinct, as most of the ubiquitinated H2A is depleted upon lost of Ring1B [31,35]. Structural analysis revealed that Ring1B interacts with Bmi-1 via their Ring fingers [33,34]. The PRC1 Ring finger proteins also share a conserved C- terminal region [36,37] that seems to be implicated in the interaction with Ph and Pc [38-40]. To gain mechanistic insight into the assembly and the enzymatic activity of the PRC1 proteins we performed a detailed computational sequence analysis of the C-terminal region of these pro- teins. Our findings result in the identification of a new ubiquitin-like domain that unveiled PRC1 Ring finger- like proteins in plants and worm. Results and discussion Detection of a new ubiquitin-like domain in the PRC1 Ring finger proteins To analyse the conserved C-terminal region of the Ring finger PRC1 proteins, we first performed BLAST searches [41] against different sequence databases located at Uni- Prot [42], NBCI [43], ENSEMBL [44] and JGI [45], starting from the human Bmi-1. Alignments were generated with T-Coffee [46] and checked manually. Additional profile- based sequence searches were performed against the Uniref50 and Uniref 90 protein sequence databases [47] with the defined global hidden Markov models using HMMer [48]. Using extensive profile to sequence (HMMer) and profile to profile comparisons analyses [49] we identified statistically significant E-values of sequence similarity between the C-terminal conserved regions of PRC1 Ring finger proteins and the C-terminal region of the WDR48-p80 protein family (Figure 1 and 2). The WD repeat domain 48 or p80 (WDR48-p80) family are WD40 repeat-containing endosomal proteins found in all eukaryotes including yeast and are present in only one copy per organism (Figure 1 and 3). Except for the previously described interaction between the human WDR48-p80 protein and a tyrosine kinase interacting pro- tein from Herpesvirus saimiri virus (Tip), the exact function of the WDR48-p80 family remains unknown but has been Page 2 of 11 (page number not for citation purposes)