Table 2.
The top 20 enrichment-ranked TRANSFAC v9.3 TFBS models that co-occurred within ±250 bp of Foxa2-binding sequences within peaks or occurred in within ±250 bp of a peak maximum in peaks without Foxa2 sites
| TFBS model | Model # | No. of peaks | Z-score | TF in liver? | No. of genes | Level 5 GO Biological Process | Percentage (%) |
|---|---|---|---|---|---|---|---|
| Peaks with exact FoxA2 sequence | |||||||
| FOX_Q2 | M00809 | 995 | 231.3 | Family | 621 | Cellular metabolic process | 25.0 |
| PAX6_Q2 | M00979 | 138 | 161.3 | No | 102 | Biopolymer modification/Cellular protein metabolic process | 29.0 |
| HFH3_01 | M00289 | 448 | 140.9 | No | 302 | RNA metabolic process/Cellular protein metabolic process | 21.4 |
| MAZR_01 | M00491 | 139 | 106.3 | Yes (PCR) | 83 | RNA metabolic process | 30.8 |
| HNF3B_01 | M00131 | 569 | 82.4 | Yes (tag) | 340 | Cellular protein metabolic process | 26.2 |
| HNF4_Q6_01 | M01031 | 791 | 58.8 | Yes (tag) | 462 | Cellular protein metabolic process | 24.0 |
| MAZ_Q6 | M00649 | 245 | 56.8 | Yes (tag) | 162 | Regulation of cellular metabolic process | 29.4 |
| HNF4_DR1_Q3 | M00764 | 754 | 53.3 | Yes (tag) | 462 | RNA metabolic process | 22.9 |
| SMAD3_Q6 | M00701 | 97 | 44.0 | Yes (PCR) | 64 | Cellular protein metabolic process | 33.3 |
| COUPTF_Q6 | M01036 | 479 | 43.8 | Family | 270 | Cellular protein metabolic process | 21.3 |
| PAX_Q6 | M00808 | 706 | 41.5 | Family | 433 | Cellular protein metabolic process | 26.5 |
| HNF1_Q6 | M00790 | 844 | 41.2 | Yes (tag) | 465 | Regulation of cellular metabolic process | 21.5 |
| GATA4_Q3 | M00632 | 1285 | 37.6 | Yes (tag) | 700 | Cellular protein metabolic process | 24.9 |
| HNF1_C | M00206 | 1029 | 34.8 | Yes (tag) | 549 | Cellular protein metabolic process | 29.7 |
| EVI1_04 | M00081 | 1028 | 33.5 | Yes (PCR) | 565 | Cellular protein metabolic process | 25.9 |
| PPARG_03 | M00528 | 522 | 32.2 | Yes (tag) | 310 | RNA metabolic process | 19.3 |
| LDSPOLYA_B | M00317 | 240 | 30.5 | No | 129 | RNA metabolic process | 28.8 |
| FREAC2_01 | M00290 | 34 | 30.5 | No | 23 | Regulation of cellular metabolic process/RNA metabolic process/Transcription | 43.8 |
| KROX_Q6 | M00982 | 13 | 29.0 | Family | 11 | Cell surface receptor linked signal transduction | 50 |
| FOXJ2_01 | M00422 | 124 | 27.6 | Yes (tag) | 75 | RNA metabolic process/Regulation of cellular metabolic process | 23.2 |
| Peaks with no FoxA2 sequence | |||||||
| MAZR_01 | M00491 | 138 | 82.9 | Yes (PCR) | 77 | Cellular protein metabolic process | 29.2 |
| PAX6_Q2 | M00979 | 69 | 57.0 | No | 44 | Intracellular signaling cascade | 31.8 |
| MAZ_Q6 | M00649 | 269 | 47.0 | Yes (tag) | 164 | RNA metabolic process/Transcription/Regulation of cellular metabolic process | 31.2 |
| KROX_Q6 | M00982 | 25 | 39.0 | Family | 20 | Regulation of cellular metabolic process/RNA metabolic process/Transcription/Cellular protein metabolic process | 33.3 |
| HNF4_Q6_01 | M01031 | 576 | 21.7 | Yes (tag) | 361 | Cellular protein metabolic process | 25.7 |
| UF1H3BETA_Q6 | M01068 | 2 | 19.9 | No | 1 | 15 different termsa | 100 |
| HNF4_DR1_Q3 | M00764 | 537 | 17.4 | Yes (tag) | 321 | Cellular protein metabolic process | 21.9 |
| SMAD3_Q6 | M00701 | 51 | 15.5 | Yes (PCR) | 31 | Intracellular signaling cascade/RNA metabolic process | 19.2 |
| NRF1_Q6 | M00652 | 5 | 14.9 | Yes (tag) | 6 | Response to oxidative stress/Carboxylic acid metabolic process/Cellular protein metabolic process/Mitochondrion organization and biogenesis/Macromolecule biosynthetic process/DNA metabolic process | 33.3 |
| COUPTF_Q6 | M01036 | 333 | 14.7 | Family | 225 | Cellular protein metabolic process | 26.6 |
| MIF_01 | M00279 | 6 | 12.3 | Yes (PCR) | 4 | Cytoskeleton organization and biogenesis/Establishment of cellular localization | 100 |
| SMAD4_Q6 | M00733 | 46 | 11.8 | Yes (tag) | 29 | Phosphate metabolic process/Cellular protein metabolic process | 28.6 |
| ATF_B | M00338 | 4 | 11.7 | Family | 3 | RNA metabolic process/Regulation of cellular metabolic process/Transcription | 100 |
| PPARG_03 | M00528 | 423 | 11.1 | Yes (tag) | 246 | Cellular protein metabolic process | 24.8 |
| PAX_Q6 | M00808 | 483 | 10.9 | Family | 287 | Cellular protein metabolic process | 30.9 |
| SF1_Q6 | M00727 | 118 | 10.9 | Yes (tag) | 83 | Regulation of cellular metabolic process | 32.6 |
| BRN2_01 | M00145 | 75 | 10.8 | No | 21 | Regulation of cellular metabolic process | 50 |
| RREB1_01 | M00257 | 9 | 10.4 | Yes (tag) | 7 | Regulation of cellular metabolic process/RNA metabolic process/Transcription | 50 |
| SP3_Q3 | M00665 | 59 | 10.0 | Yes (tag) | 36 | Cellular protein metabolic process | 47.6 |
| LHX3_01 | M00510 | 11 | 8.3 | No | 5 | Regulation of cellular metabolic process/RNA metabolic process/Transcription | 66.7 |
Included in the table are: (i) the number of peaks that contained the TFBS model; (ii) the Z-score, which represents the difference between the MATCH v2.6 PWM scan enrichment of real peak sequences and the mean for randomized sequences, divided by the standard deviation for randomized sequences (see Methods section); (iii) an indication of whether the transcription factor is expressed in the adult liver, based either on SAGE tag(s) from our adult liver library or RT–PCR amplification in the adult liver; (iv) the number of annotated genes that contained at least one peak within its extended gene region (10 kb upstream of the TSS to 1 kb downstream of the TTS); (v) the ‘level 5’ Gene Ontology Biological Process category assigned to the largest subgroup within these gene groups and (vi) the corresponding percentage of genes in the subgroup. TFBS models that co-occurred with a Foxa2-binding sequence included both transcription factors that have previously been demonstrated to interact with Foxa2 (HNF4 and members of the Coup-TF family) and also novel potential interacting transcription factors (Smad3 and Maz). Ten of the TFBS models that co-occurred with Foxa2-like binding sequences in peaks containing such sequences also occurred in peaks that did not contain Foxa2-like binding sequences.
aRegulation of biological process; cellular metabolic process; macromolecule metabolic process; primary metabolic process; cell organization and biogenesis; regulation of metabolic process; regulation of cellular process; organelle organization and biogenesis; biopolymer metabolic process; nucleobase, nucleoside, nucleotide and nucleic acid metabolic process; chromosome organization and biogenesis; regulation of cellular metabolic process; RNA metabolic process; transcription; DNA metabolic process.