Table 2.
The most hydroxymethylated loci in prefrontal cortex and cerebellum are enriched in distinict genomic regions
| Loci with detectable 5hmC in brain (%) | 1,000 loci with highest 5hmC in prefrontal cortex | 1,000 loci with highest 5hmC in cerebellum | |||||
|---|---|---|---|---|---|---|---|
| Detectable 5hmC sites (%) | Enrichment (95 % CI) | P value | Detectable 5hmC sites (%) | Enrichment (95 % CI) | P value | ||
| All probes (N = 79,263) | 1,000 | - | - | 1,000 | - | - | |
| CpG island feature | |||||||
| Island | 7,837 (9.9 %) | 121 (12.1 %) | 1.25 (1.03–1.52) | 0.022 | 275 (27.5 %) | 3.46 (2.99–3.99) | 7.01E-55 |
| Shore | 22,593 (28.5 %) | 472 (47.2 %) | 2.24 (1.97–2.55) | 3.19E-35 | 276 (27.6 %) | 0.96 (0.83–1.10) | 0.549 |
| Shelf | 11,674 (14.7 %) | 93 (9.3 %) | 0.59 (0.47–0.74) | 4.29E-07 | 121 (12.1 %) | 0.80 (0.65–0.97) | 0.019 |
| Outside | 36,342 (45.8 %) | 307 (30.7 %) | 0.52 (0.46–0.60) | 3.37E-22 | 326 (32.6 %) | 0.57 (0.50–0.65) | 2.94E-17 |
| Unannotated | 817 (1.0 %) | 7 (0.7 %) | 0.68 (0.27–1.41) | 0.426 | 2 (0.2 %) | 0.19 (0.02–0.70) | 3.94E-03 |
| Gene feature | |||||||
| Intergenic | 9,604 (12.1 %) | 89 (8.9 %) | 0.71 (0.56–0.88) | 1.48E-03 | 74 (7.4 %) | 0.58 (0.45–0.74) | 1.56E-06 |
| Distal promoter | 3,703 (4.7 %) | 46 (4.6 %) | 0.98 (0.71–1.33) | 1.000 | 19 (1.9 %) | 0.40 (0.24–0.62) | 4.88E-06 |
| Proximal promoter | 16,979 (21.4 %) | 365 (36.5 %) | 2.11 (1.85–2.40) | 3.10E-27 | 206 (20.6 %) | 0.95 (0.81–1.11) | 0.561 |
| Gene body | 46,238 (58.3 %) | 474 (47.4 %) | 0.64 (0.57–0.73) | 5.30E-12 | 670 (67.0 %) | 1.45 (1.27–1.66) | 2.60E-08 |
| Downstream | 1,922 (2.4 %) | 19 (1.9 %) | 0.78 (0.47–1.23) | 0.350 | 29 (2.9 %) | 1.20 (0.80–1.74) | 0.351 |
| Unannotated | 817 (1.0 %) | 7 (0.7 %) | 0.68 (0.27–1.41) | 0.426 | 2 (0.2 %) | 0.19 (0.02–0.70) | 3.94E-03 |
| Transcription factor binding Site | 25,482 (32.1 %) | 545 (54.5 %) | 2.53 (2.22–2.87) | 2.57E-47 | 383 (38.3 %) | 1.31 (1.15–1.49) | 4.97E-05 |
| Dnase 1 hypersensitivity site | 8,155 (10.3 %) | 150 (15 %) | 1.54 (1.28–1.84) | 3.95E-06 | 143 (14.3 %) | 1.45 (1.21–1.74) | 8.42E-05 |
| Alternative transcription events (N = 30,659 probes) | 398 | - | - | 451 | - | - | |
| A3SS | 798 (2.6 %) | 8 (2.0 %) | 0.77 (0.33–1.54) | 0.632 | 22 (4.9 %) | 1.92 (1.18–2.96) | 6.74E-03 |
| A5SS | 827 (2.7 %) | 12 (3.0 %) | 1.12 (0.57–1.90) | 0.640 | 17 (3.8 %) | 1.41 (0.81–2.30) | 0.185 |
| AFE | 9,159 (29.9 %) | 158 (39.7 %) | 1.55 (1.25–1.90) | 3.41E-05 | 112 (24.8 %) | 0.78 (0.62–0.96) | 0.020 |
| ALE | 3,017 (9.8 %) | 27 (6.8 %) | 0.67 (0.43–0.99) | 0.041 | 46 (10.2 %) | 1.04 (0.75–1.42) | 0.811 |
| CE | 16,604 (54.2 %) | 185 (46.5 %) | 0.74 (0.60–0.90) | 2.37E-03 | 208 (46.1 %) | 0.72 (0.60–0.88) | 7.17E-04 |
| CNE | 3,755 (12.2 %) | 53 (13.3 %) | 1.10 (0.81–1.48) | 0.490 | 62 (13.7 %) | 1.14 (0.86–1.50) | 0.347 |
| EI | 50 (0.2 %) | 1 (0.3 %) | 1.54 (0.04–9.04) | 0.482 | 2 (0.4 %) | 2.73 (0.32–10.43) | 0.174 |
| II | 6,003 (19.6 %) | 89 (22.4 %) | 1.18 (0.92–1.50) | 0.163 | 87 (12.3 %) | 0.98 (0.77–1.25) | 0.952 |
| IR | 3,529 (11.5 %) | 63 (15.8 %) | 1.45 (1.08–1.90) | 0.011 | 80 (17.7 %) | 1.66 (1.28–2.12) | 1.08E-04 |
| MXE | 3,814 (12.4 %) | 43 (10.8 %) | 0.85 (0.61–1.17) | 0.259 | 35 (7.8 %) | 0.59 (0.41–0.84) | 1.90E-03 |
The level of enrichment of the top 1,000 loci in each brain region was determined by Fisher’s exact test. 5hmC, 5-hydroxymethylcytosine; CI, confidence interval; A3SS, alternative 3’ splice site; A5SS, alternative 5’ splice site; AFE, alternative first exon; ALE, alternative last exon; CE, cassette exon; CNE, constitutive exon; EI, exon isoforms; II, intron isoforms; IR, intron retention; MXE, mutually exclusive exon