Table 1.
organisms compared | tissue/cell line or type | transcription factor/histone modification | conservation level of binding/histone modification region or putatively bound genes | reference conservation level of binding/histone modification region or putatively bound genesa | notes | reference |
---|---|---|---|---|---|---|
D. melanogaster, D. yakuba (6.5 Myr) | whole embryo (collected within 1 h preceding gastrulation) | bcd (bicoid) hb (hunchback) Kr (Kruppel) gt (giant) kni (knirps) cad (caudal) |
98–99% 85–97% 97–99% 98–99% 97–100% 98–99% |
— binding intensities presented differences for all six TFs — stronger binding events are less conserved — suggested an epigenetic cause for correlated binding intensity differences |
[26] | |
D. melanogaster, D. annanassae (44.2 Myr), D. erecta (12.8 Myr), D. pseudoobscura (33.6 Myr), D. yakuba (6.5 Myr) |
whole embryo (approx. 2–4 h after egg laying) | twi (twist) sna (snail) |
approximately 80% (D. mel versus D. sim and yakuba) 57–65% (D. mel versus all other) 34% shared across all 6 species approximately 91% (D. mel versus D. sim) |
98% D. mel twi biological replicate 88% D. mel sna biological replicate |
— clustering using the differences among binding maps recapitulated the known phylogenetic tree — observed differences in binding intensities — conservation of binding is higher for genes with functions related to the known role of twi — approximately 50% of binding events assigned to genes downregulated in twi knockouts are conserved, whereas conservation is lower than average for binding events near genes unresponsive to twi knockout. |
[41] |
S. cerevisiae, S. mikatae (5–20 Myr [42]), S. bayanus (14.3 Myr) | all species kept under low-nitrogen condition (pseudo-hyphal growth) | Ste12 Tec1 |
21% 20% (genes putatively bound in three species) |
97% 95% (genes shared between biological replicates) |
— observed differences in binding intensity — different functions for conserved and species-specific putatively bound genes |
[14] |
two yeast strains: S. cerevisiae strains S96 and HS959 | grown in presence and absence of mating pheromone α-factor | Ste12 | approximately 70% of the genes between S96 and HS959 | >0.96 mean Pearson correlation between biological replicates, <0.89 between strains | — approximately 78% of the variable binding regions exhibit Mendelian segregation — several cases of transgression were noted — 35% of the motifs in cis-variable binding traits were affected by variation versus 1% of the non-variable |
[25] |
S. cerevisiae, K. lactis (>100 Myr [43]), C. albicans (489.8 Myr) | — | Mcm1 | 7–42% (genes), 13–18% (genes in three species) | duplicates were pooled | — genes bound in all three species are enriched for cell cycle and mating type. Species-specific targets have new functions | [15] |
six human individuals (one trio from CEU and one from YRI) | lymphoblastoid cell lines | CTCF | 82% (all six individuals), approximately 99% within populations | — 11% of the sites are allele-specific | [24] | |
10 human individuals | lymphoblastoid cell lines | NFKB Pol II |
92.5% 75% NFKB: 94% TSSb, 92% non-TSS Pol II: 75% TSSb, 72% non-TSS |
Pol II 68% between humans and chimpanzee | — Pol II binding events: 79% Mendelian, 5% transgression. NKFB binding events: 68% Mendelian, 4% transgression — 35% of the NFKB and 26% Pol II divergent binding events coincided with genetic variations — Spearman correlation between gene expression and NFKB: 0.475 and Pol II: 0.461 — stronger binding events are more often conserved — distinct functions associated with common versus species-specific events |
[23] |
human, mouse (mutant mouse contains a human chromosome 21) (92.3 Myr) | liver | HNF1A HNF4A HNF6 H3K4me3 |
18% 34% 14% 91% (TSS), 32% (non-TSS) |
— mouse chromosome 16 in mutant versus wild-type mouse: 95–100% — human chromosome 21 in mouse versus in human: 86% HNF1A 82% HNF4A 74% HNF6 86% H3K4me3 (TSS) 78% H4K4me3 (non-TSS) |
— used a Down syndrome mouse model to control for experimental and species-specific differences | [16] |
human, mouse (92.3 Myr) | liver | FOXA2 HNF1A HNF4A HNF6 |
11–45% (genes) 18–20% (genes) 31–59% (genes) 13–27% (genes) |
HNF6: 66% of the genes bound in human liver were bound in HepG2 | [17] | |
human, mouse (92.3 Myr) | ESCs | OCT4 NANOG CTCF |
2%, 3.8%c 1.9%, 5.3%c 16.7%, 49.6%c |
— 11/137 genes downregulated in OCT4 knockouts in mouse and human had a nearby OCT4–NANOG binding event — 62/137 genes were cases of turnover — 55/137 of these genes had no binding events — 82-fold enrichment for overlap of OCT4 sites with LTR9B repeats — binding events overlapping repeats: 20.9% for OCT4, 14.6% for NANOG and 11.1% for CTCF in human and 7.2%, 17.1% and 28.3% in mouse — two LTR9B (repeat) binding regions were validated as enhancers |
[18] | |
human, mouse (92.3 Myr) | ESCs | OCT4 NANOG |
9.1% (genes) 13% (genes) — 14% of OCT4 peaks <10 kb of the TSS — 21% of NANOG peaks <10 kb of the TSS |
— data compared were generated by different studies and platforms (human data from [44]) | [19] | |
human, mouse (92.3 Myr) | human liver, HepG2, islets, acinar; mouse liver, spleen, kidney, brain, testes, pancreatic islets, pancreatic acinar and Min6 | E2F4 | 20% (genes) | genes overlapping among mouse tissues >65–85% of the genes putatively bound; among human tissues: 70–84% | — did not find a relationship between genes downregulated upon E2F4 knockout — approximately 50 genes with nearby E2F4 binding conserved, GO enrichment for cell cycle, proliferation and DNA repair functions. DNA packaging enriched in mouse-only binding events |
[20] |
human, mouse (92.3 Myr) | human adipose stromal cells versus 3T3-L1 mouse adipocytes | CTCF PPARG H3K4me3, H3K4me1, H3K4me2, H3K27ac |
approximately 53% (L1) 21% (L1) approximately 15–30% (>2kb from TSS) |
— species-specific histone marks were associated with species-specific expression — histone conservation was higher near the TSS and increased with enrichment of the peaks — conservation near TSS decreases with enrichment for PPARG and CTCF — cases of turnover observed |
[21] | |
human, mouse (92.3 Myr), chicken (296 Myr) | human CD4+, HeLa and Jurkat cells; mouse ESCs and embryonic fibroblasts; chicken 5- and 10-day-old red blood cells | CTCF | 7% of the chicken sites (or 2% of the mouse sites) found in both red blood cell are conserved in all three species | conservation within species (% of the largest set): mouse tissues: 27% human cells: 36% chicken: 16% |
— only sites that were present in all cells of each species and across species were considered | [45] |
human, chimpanzee (6.3 Myr) | lymphoblastoid cell lines | H3K4me3 | 69.5±0.3% (human–chimpanzee) 63.9±0.4% (human–rhesus) 63.2±0.3% (chimpanzee–rhesus) |
overlap within the same species: 77.7±0.4% | — estimated that at most 7% of gene expression differences between human, chimpanzee and 3% between chimpanzee and rhesus correlated with differences in H3K4me3 — conservation was higher for peaks <1kb of the TSS |
[46] |
human, mouse (92.3 Myr) | various | H3K4me1 H3K4me3 H3K27ac |
approximately 20–40% approximately 80% TSSb, >approximately 10–40% non-TSS approximately 80% TSSb, >approximately 20–40% non-TSS |
— data compared were generated by different studies and platforms — conserved fraction was higher near TSS — conservation increased when regions were present in multiple cell types — fraction of conserved regions increased with number of transcription factors bound |
[22] | |
human, mouse (92.3 Myr), dog (94.2 Myr), opossum (162.6 Myr), chicken (296 Myr) | liver | CEBPA | 2% human–chicken 7% human–opossum 13% human–mouse 0.3% (all five species) |
71% human–human 66% mouse–mouse 61% dog–dog 57% opossum–opossum 56% chicken–chicken |
— binding events conserved in at least two species are more likely to occur near genes that are differentially expressed upon knockout of CEPBA/HNF4A — no correlation between binding intensity and conservation — observed many cases of turnover events — 20–40% of the motifs located in species-specific binding events were intact. A ‘larger fraction’ of the motifs were found to be disrupted |
[47] |
human, mouse (92.3 Myr), dog (94.2 Myr) | liver | HNF4A | 12% human–mouse 9% human–dog |
72% human–human 77% mouse–mouse 63% dog–dog |
[47] | |
human, chimpanzee (6.3 Myr) | lymphoblastoid cell lines | Pol II | 68% | — species-specific events were associated with different functions than conserved events — higher conservation for stronger Pol II binding events |
[23] |
aData in this column can be used to assess the significance of the divergence shown in the previous column. When available, the data reports the conservation level in a ‘reference’ group, such as between biological replicates or between different tissues of the same species, or different species when the previous column refers to a comparison within the same species. For example, a 20% conservation level between species is not surprising if replicates shown 20% conservation only.
b<1kb of the TSS.
cTop 10% binding events.