BMC Genomics 2009, 10:576 http://www.biomedcentral.com/1471-2164/10/576 YFYig1uDreN3A-binding motifs as translated dipeptides YY1 DNA-binding motifs as translated dipeptides. The four base pair core motif of the YY1 binding site is CCAT (for- ward) and ATGG (reverse). In principle, this core can code for two codons in each of the three frames. In the forward direc- tion, CCAT can encode 29 possible dipeptides while in the reverse direction ATGG can encode 21 dipeptides, with one duplicate. These 49 dipeptides are a subset of the 400 possible dipeptides which can be found in a protein (20 total amino acids)2. The distribution frequency of these dipeptides has been examined to determine if any of the 49 YY1 binding sites is overrepresented in olfactory receptor genes. their protein-coding regions (Figures 1&2). Statistical analyses further confirmed that this enrichment of YY1 binding motifs is consistent with functional relevance and has likely been driven by unknown selection pressure at the DNA level. Overall, the current study suggests a poten- tial role of YY1 or YY1-related transcription factors in the regulation of the mammalian OLFR genes. Also, this study provides further evidence that the protein-coding regions of vertebrate genes can both encode codon information and contain cis-regulatory elements for transcription fac- tor binding. The mammalian OLFR genes are expressed primarily in olfactory neurons, and only one single copy (allele) out of the entire 1,000 family members is expressed and func- tional in a given neuron cell [20]. This highly tissue-spe- cific expression pattern of the OLFR genes necessitates a global repression mechanism for the majority of the OLFR genes in neural cells and in the other cell types. This mech- anism acts prior to, and is separate from the negative feed- back which prevents bi- and multi-allelic expression in olfactory neurons [29,30]. Since unknown mechanisms are believed to repress a large number of the OLFR genes all the time in most of the cell types, it is likely that these repression mechanisms are mediated through epigenetic modifications. Since YY1 is a well-known epigenetic regu- lator in the animal genome, it is plausible to propose that the identified YY1 binding motifs may play some roles in the predicted repression mechanisms for the OLFR genes [3]. In that regard, it is important to note that YY1 is one of the Polycomb group Gene (PcG) members found in both invertebrates and vertebrates [2]. Furthermore, recent studies hinted at the possibility that PcG-mediated repression mechanisms might be involved in the regula- tion of the OLFR genes [31]. In mutant mouse embryonic stem cells lacking the embryonic ectoderm development (EED) protein, some OLFR genes do not replicate asyn- chronously as they differentiate, suggesting a loss of the typical pattern of monoallelically expressed genes [32]. According to the results from another recent study, some cis-regulatory elements responsible for selecting one active OLFR copy in a given neuron cell are predicted to be Page 6 of 10 (page number not for citation purposes)