Comparative sequence analysis of the MECP2-locus in human and mouse reveals new transcribed regions

Comparative sequence analysis facilitates the identification of evolutionar ily consented regions, that is, gene-regulatory elements, which can not be detected by analyzing one species only. Sequencing of a 152-kb region on hu man Chromosome (Chr) Xq28 and of the synthenic 123 kb on mouse Chr XC ident ified the MECP2/Mecp2 locus, which is flanked by the gene coding for Interl eukin-1 receptor associated kinase (IRAK/Il1rak) and the red opsin gene (RC P/Rsvp). By comparative sequence analysis, we identified a previously unkno wn, non-coding 5' exon embedded in a CpG island associated with MECP2/Mecp2 . Thus, the MECP2/Mecp2 gene is comprised of four exons instead of three. F urthermore, sequence comparison 3' to the previously reported polyadenylati on signal revealed a highly conserved region of 8.5 kb terminating in an al ternative polyadenylation signal. Northern blot analysis verified the exist ence of two main transcripts of 1.9 kb and similar to 10 kb, respectively. Both transcripts exhibit tissue-specific expression patterns and have almos t identical short half-lifes. The similar to 10-kb transcript corresponds t o a giant 3' UTR contained in the fourth exon of MECP2. The long 3' UTR and the newly identified first intron of MECP2/Mecp2 are highly conserved in h uman and mouse. Furthermore, the human MECP2 locus is heterogeneous with re spect to its DNA composition. We postulate that it represents a boundary be tween two H3 isochores that has not been observed previously.