Quest for epigenetic determinants of local coexpression clusters Wieslawa Mentzen Labrador and Corces, 2002.

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Quest for epigenetic determinants of local coexpression clusters Wieslawa Mentzen Labrador and Corces, 2002

Expression of genes that are immediate neighbors on the chromosome is correlated more often than expected by chance Found also in human, yeast, Drosophila, C.elegans It is very week effect (<2 % of genes), and short-distance (up to 10 genes) Coexpression stronger between closer genes Orientation matters (lowest coexpression between convergent orientation -><-) Hypotheses -tandem duplicates -eukaryotic operons -sharing of regulatory cis-elements -sharing chromatine domains Coexpression of neighboring genes

No TRIncluding TR

Are epigenetic modifications responsible for observed coexpression? Focus on the methylation and acetylation of histones, as these modifications are associated with transcriptional activity of genes Specifically 1.Do the genes in a coexpressed pair share similar pattern of chromatin modification? 2. Do the genes that participate in coexpressed neighbor groups differ from other genes in their pattern of chromatin modification? histone DNA strand acetylated Lysine

Chip-seq data for pattern of methylation of H3K9 Format: 3 mln probes (25-mer), spaced ca every 35 nucleotides. For each probe, VALUE shows the probability of methylation (0 is negative and 1 is positive for methylation) 25nt Zhang et al, Genome-wide analysis of mono- di- and trimethylation of histone H3 lysine 9 in Arabidopsis thaliana Genome Biology 2009, 10:R62

Histone methylation patterns of genes Additionally, in the same way, presence of methylation in promoter sequence of each gene (-200bp to 0bp) was recorded Every gene represented by a binary sequence, eg mono di tri promoterORF Hamming distance: number of different bits.

Hamming distances, genes from all chromosomes Adjacent Coexpressed 65 pairs Adjacent Not coexpressed 1000 pairs Not adjacent Not coexpressed 1000 pairs Similarity of histone methylation patterns of gene pairs Distance between methylation profiles of genes in a pair Not adjacent Coexpressed 1000 pairs Adjacent genes have similar methylation patterns, irrespective of coexpression.

New data: 1. trimethylation of H3 Lysine K27 2. acetylation of H3 Lysine K9 3. acetylation of H3 Lysine K27 Of previous data (mono- di- and trimethylation of histone H3 Lysine 9 in ORF and promoter regions) 4. trimethylation of H3 Lysine K9 Histone modification patterns of genes

Adjacent non-coexpressed Adjacent coexpressed Non-adjacent coexpressed Non-adjacent non-coexpressed Chromosome 1 Similarity of histone modification patterns of gene pairs Distance btw modifications in genes in a pair cng genes all genes K9me1 K9me2K9me3K27me3K9acK27ac Average profile of modification

Adjacent non-coexpressed Adjacent coexpressed Non-adjacent coexpressed Non-adjacent non-coexpressed Chromosome 2 Distance btw modifications in genes in a pair cng genes all genes K9me1 K9me2K9me3K27me3K9acK27ac Similarity of histone modification patterns of gene pairs Average profile of modification

Adjacent non-coexpressed Adjacent coexpressed Non-adjacent coexpressed Non-adjacent non-coexpressed Chromosome 3 Distance btw modifications in genes in a pair cng genes all genes K9me1 K9me2K9me3K27me3K9acK27ac Similarity of histone modification patterns of gene pairs Average profile of modification

Adjacent non-coexpressed Adjacent coexpressed Non-adjacent coexpressed Non-adjacent non-coexpressed Chromosome 4 Distance btw modifications in genes in a pair cng genes all genes K9me1 K9me2K9me3K27me3K9acK27ac Similarity of histone modification patterns of gene pairs Average profile of modification

Adjacent non-coexpressed Adjacent coexpressed Non-adjacent coexpressed Non-adjacent non-coexpressed Chromosome 5 Distance btw modifications in genes in a pair cng genes all genes K9me1 K9me2K9me3K27me3K9acK27ac Similarity of histone modification patterns of gene pairs Average profile of modification

Adjacent non-coexpressed Adjacent coexpressed Non-adjacent coexpressedNon-adjacent non-coexpressed Pooled data from all chromosomes Distance btw modifications in genes in a pair Similarity of histone modification patterns of gene pairs A/nC nA/nC nA/C A/nCA/CnA/nC Adjacent genes have similar histone modification patterns, irrespective of coexpression. P-value for difference of means

Similarity of histone modification patterns of gene pairs vs their distance on chromosome distance between genes on chromosome Average distance btw modification profiles

What next? Which modifications contribute most to the similarity? Look at the data at higher resolution, i.e. presence of modifications in the particular regions of genes: promoter, upper half, lower half Is the similarity of modifications constrained to chromosomal domains of the same transcriptional activity?