Università degli Studi di Milano. Member of LERU (League of European Research Universities). 1° University in Italy for scientific productivity (Leiden ranking 2012). 1° University in Italy in Biomedical Sciences. Dipartimento di Bioscienze 90 Faculty members, 6 EMBO Members. Genetics, Molecular Biology, Structural Biology, Biochemistry, Bioinformatics, Developmental Biology, Physiology, Plant Biology, Ecology. PhD program in Biomolecular Sciences. 50 students. Joint PhD program with EMBL, Heidelberg. Progenitor cells Pancreatic cell Endoderm Hepatocyte ES cell Myoblast Mesoderm B cell Totipotent cell Ectoderm Neuron Epithelial cell Pluristratified NF-Y-DNA structure NF-YA/NF-YB/NF-YC interface • A1 helix contacts extensively NF-YB/NF-YC (1760 Å2) • heterotrimerization through side-chain and backbone polar interactions • A1A2-linker: extended conformation that directs A2 helix towards the DNA A T A1 helix A C K261 A2 P263 C E52 R266 Y56 F50 E82 Q85 E86 I117 R253 D116 a2(YB) aC(YC) a1(YC) R249 E90 S93 S97 F113 R250 R245 F94 Q110 I246 F125 D112 V238 A1 Q242 E98 E101 L123 T122 D109 N239 K241 S121 The genomic strategy of NF-Y: The ENCODE Project. ChIp-Seq/Mass-Spec in 9 cell types of 10 histone PTMs and 72 -and countingDNA-binding Proteins (Mostly TFs). Clustering NF-Y with 80 nuclear proteins. Actual Overlap % of NFYB bound Promoters Fisher Exact Test 51,916 3788 Expected Overlap n= n- # Enhancers (all) with Factor 21,641 3914 # Peaks in Enhancers (all) n= n= 14,404 2,943 20,895 9,303 20,609 11,024 23,586 11,589 15,401 4,337 17,951 4,718 18,815 9,921 13,693 7,222 14,496 9,305 29,410 10,436 9,862 7,287 6,402 2,667 6,932 3,296 9,229 5,400 5,025 2,915 16,358 5,170 2,475 1,594 18,480 3,733 21,313 2,746 10,662 6,203 9,860 2,412 5,250 3,107 3,328 2,181 10,746 3,779 3,020 1,592 2,701 1,180 44,168 3,215 1,623 602 10,004 2,765 19,094 3,194 885 415 939 486 5,576 494 8,031 2,459 46,476 6,027 1,136 338 1,606 501 945 323 8,379 1,032 3,397 416 1,839 277 11,209 1,770 24,841 2,681 2,514 578 3,477 439 8,061 1,369 8,128 1,444 612 237 2,607 460 5,514 502 25,479 1,454 3,924 265 4,126 551 2,174 477 4,530 368 1,057 203 9,025 1,039 2,005 222 1,245 262 17,914 890 2,075 480 6,616 618 8,572 971 17,401 1,424 3,182 328 4,536 335 317 173 1,794 246 5,715 286 520 251 23,337 2,689 563 219 67 12 8,831 498 11,393 571 2,969 126 10,209 643 12,314 48 794 3 201 5 # Genomic Peaks cFOS CCNT2 E2F6 POL2 ORC2 ELF1 HMGN3 cMYC TBP ps2-POL2 E2F4 MAX CHD2 HEY1 GABP BHLHE40 GTF2B cJUN USF1 TFIIF HDAC8 YY1 NRF1 BRD4 MXI1 SIN3A CEBPB USF2 TFIIIC EGR1 GTF2F1 ATF3 SP1 ZBTB7A CTCF NELFE THAP1 JUND SETDB1 SIX5 SPT5 BRG1 TAL1 STAT2_30m NFE2 INI1 ZNF263 TR4 ETS1 NR4A1 PU1 BCL3 TAF1 STAT2_6h ZBTB33 STAT1_30m GATA2 SRF STAT1_6h MAFK RPC155 BCLAF CTCFL RAD21 GATA1 TAF7 BRF1 SIRT6 NRSF BDP1 SMC3 POL3 BRF2 HDAC2 FOSL P300 MEF2A KAP1 ZNF274 XRCC4 Overlapping Factor <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 2.4E-285 5.3E-199 4.4E-179 3.3E-173 1.8E-171 1.4E-138 5.2E-131 1.3E-118 3.1E-117 2.7E-115 5.2E-114 2.9E-104 1.0E-85 2.7E-85 1.1E-82 1.6E-81 6.7E-71 7.4E-63 1.1E-62 1.6E-55 1.2E-54 1.9E-53 6.7E-39 1.7E-38 3.1E-37 1.4E-29 2.0E-24 9.2E-23 1.0E-22 3.6E-21 5.3E-20 1.5E-18 1.9E-15 2.7E-14 1.8E-12 1.1E-11 5.2E-09 1.0E-07 7.6E-08 3.8E-06 1.0E-05 3.5E-05 1.3E-04 1.7E-04 1.9E-04 5.3E-04 4.7E-04 2.1E-03 3.3E-03 4.1E-02 1.4E-02 1.6E-02 2.0E-02 4.6E-02 3.9E-02 4.6E-02 2.5E-01 2.5E-01 1.0E-01 7.4E-02 4.6E-01 5.6E-01 1.8E-01 3.9E-01 7.2E-01 5.8E-01 5.5E-01 6.2E-01 1.0E+00 1.0E+00 Fisher Exact Test 65 58 41 57 67 78 69 86 80 74 43 33 37 34 26 29 39 16 23 25 24 22 23 25 19 14 19 5 7 11 28 19 4 13 4 4 13 5 7 3 3 7 5 4 4 3 2 2 2 8 2 2 2 1 1 4 2 5 6 9 1 1 2 4 2 1 4 4 1 0 1 2 0 1 1 0 0 0 0 0 % of NFYB bound Promoters 2,528 2,279 1,605 2,248 2,615 3,037 2,695 3,347 3,126 2,912 1,695 1,286 1,455 1,346 1,006 1,138 1,540 620 912 959 939 878 910 982 742 542 732 191 268 421 1,088 748 175 494 156 176 502 181 257 108 124 287 180 142 150 122 88 87 78 299 74 82 88 50 57 145 78 195 230 357 55 43 59 141 63 49 173 139 33 13 41 62 15 22 39 18 11 2 1 0 Actual Overlap Overlapping Factor 1,450 521 556 1,139 1,271 1,662 1,558 1,800 1,712 1,456 809 616 772 697 452 593 927 258 458 496 483 454 511 568 390 250 403 58 99 204 821 453 67 289 57 77 333 90 144 44 56 177 103 77 87 68 48 50 44 235 45 53 60 30 36 111 54 160 193 325 41 31 45 121 80 38 112 127 26 8 46 58 11 26 37 16 14 1 1 1 Expected Overlap Fisher Exact Test 20,895 8,305 14,404 2,966 6,932 3,109 13,693 6,506 9,862 7,163 20,609 9,516 18,815 8,880 23,586 10,316 29,410 9,741 14,496 8,261 9,229 4,549 15,401 3,522 16,358 4,341 17,951 3,936 6,402 2,534 18,480 3,394 10,662 5,241 2,475 1,445 21,313 2,584 5,025 2,765 9,860 2,793 5,250 2,534 44,168 2,972 10,746 3,203 3,328 2,170 3,020 1,390 10,004 2,310 5,576 324 1,623 547 2,701 1,137 46,476 4,790 19,094 2,549 885 368 24,841 1,641 1,136 317 1,606 427 8,031 1,864 939 496 11,209 830 1,839 249 945 308 8,379 997 8,061 592 3,397 431 2,514 482 3,477 380 2,607 272 2,075 282 612 241 8,128 1,327 4,530 253 4,126 297 2,174 341 4,536 170 2,005 198 5,514 636 3,924 307 17,401 898 25,479 1,093 23,337 1,835 3,182 225 1,057 170 6,616 259 17,914 676 5,715 442 1,245 211 9,025 633 8,572 709 1,794 141 317 46 10,209 261 11,393 328 563 65 12,314 147 8,831 213 520 89 2,969 75 67 7 201 7 794 9 Enhancer (all) # Promoters (all) with Factor % of NFYB bound Promoters # Genomic Peaks CCNT2 cFOS CHD2 cMYC E2F4 E2F6 HMGN3 POL2 ps2-POL2 TBP HEY1 ORC2 BHLHE40 ELF1 MAX cJUN TFIIF GTF2B USF1 GABP HDAC8 YY1 CEBPB BRD4 NRF1 MXI1 TFIIIC SP1 USF2 SIN3A CTCF EGR1 GTF2F1 TAL1 NELFE THAP1 ZBTB7A ATF3 BRG1 SPT5 JUND SETDB1 INI1 SIX5 STAT2_30m NFE2 ETS1 RPC155 TR4 ZNF263 ZBTB33 TAF1 STAT2_6h TAF7 SRF NR4A1 BCL3 RAD21 PU1 SMC3 GATA1 STAT1_30m BCLAF MAFK NRSF STAT1_6h GATA2 CTCFL SIRT6 BRF1 MEF2A FOSL POL3 KAP1 HDAC2 BDP1 P300 BRF2 XRCC4 ZNF274 # Peaks in Promoters (all) Actual Overlap 8,016 2,881 3,076 6,300 7,025 9,187 8,612 9,954 9,466 8,053 4,475 3,404 4,268 3,852 2,500 3,277 5,127 1,424 2,535 2,741 2,672 2,510 2,824 3,139 2,154 1,383 2,229 319 547 1,129 4,537 2,503 368 1,596 316 425 1,840 495 797 245 307 979 568 427 480 375 268 278 241 1,298 251 295 332 167 198 615 297 883 1,068 1,796 224 169 247 669 440 208 621 704 141 44 255 322 61 146 206 88 75 7 7 4 40/50 TFs show correlations, P value E-40 # Genomic Peaks Expected Overlap Promoters (all) # RefSeq Promoters with Factor # Peaks in RefSeq Promoters Overlapping Factor RefSeq Promoters (-2500bp, +500bp TSS) 2,914 9,217 10,944 11,497 4,258 4,692 9,854 7,138 9,206 10,386 7,230 2,641 3,283 5,352 2,912 5,149 1,576 3,703 2,738 6,134 2,387 3,092 2,174 3,718 1,588 1,171 3,161 602 2,714 3,177 415 486 491 2,443 5,919 337 500 323 1,031 415 276 1,713 2,660 576 437 1,325 1,438 237 458 500 1,439 263 544 474 368 202 1,036 221 261 888 467 592 970 1,424 328 333 163 246 286 244 2,677 196 12 493 570 126 639 48 3 5 213 673 799 839 311 342 719 521 672 758 528 193 240 391 212 376 115 270 200 448 174 226 159 271 116 85 231 44 198 232 30 35 36 178 432 25 36 24 75 30 20 125 194 42 32 97 105 17 33 36 105 19 40 35 27 15 76 16 19 65 34 43 71 104 24 24 12 18 21 18 195 14 1 36 42 9 47 4 0 0 2,075 2,015 2,462 2,714 1,123 1,198 2,167 1,919 2,499 2,546 2,153 823 1,371 1,547 835 1,132 588 914 754 1,184 663 749 595 791 466 380 655 255 532 564 156 163 159 413 763 125 146 114 209 119 94 270 363 130 104 209 212 65 90 89 188 54 86 78 65 43 126 41 45 109 65 75 108 66 42 41 22 30 32 28 166 23 3 29 37 10 45 3 0 0 55 53 65 72 30 32 57 51 66 67 57 22 36 41 22 30 16 24 20 31 18 20 16 21 12 10 17 7 14 15 4 4 4 11 20 3 4 3 6 3 2 7 10 3 3 6 6 2 2 2 5 1 2 2 2 1 3 1 1 3 2 2 3 2 1 1 1 1 1 1 4 1 0 1 1 0 1 0 0 0 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 4.2E-289 5.3E-286 4.6E-266 6.9E-264 4.1E-246 2.0E-245 1.6E-216 2.1E-206 2.2E-189 4.4E-181 1.2E-159 2.1E-145 2.8E-141 3.7E-128 4.0E-103 1.2E-91 1.3E-69 2.2E-64 2.0E-60 5.8E-60 4.2E-59 3.3E-55 2.8E-49 6.6E-48 3.9E-42 1.6E-39 2.9E-38 1.2E-33 1.0E-31 2.3E-31 2.5E-27 4.0E-26 7.9E-23 4.3E-21 5.9E-18 6.0E-15 6.7E-15 3.8E-12 1.3E-11 1.6E-11 3.1E-11 1.7E-10 2.2E-08 3.0E-08 6.7E-08 1.1E-07 6.1E-07 3.3E-06 1.5E-05 4.3E-05 3.9E-04 9.8E-04 5.8E-03 6.3E-03 1.6E-02 1.8E-02 2.4E-02 2.6E-02 5.2E-02 2.6E-01 5.2E-01 7.3E-01 8.8E-01 1.0E+00 1.0E+00 1.0E+00 cFOS USF1 E2F6 POL2 TBP E2F4 USF2 HMGN3 CCNT2 CHD2 cMYC MAX ELF1 ps2-POL2 ORC2 HEY1 BHLHE40 Cjun HDAC8 SP1 EGR1 GATA2 TAL1 ZBTB7A SIX5 GTF2B GABP TFIIF BRD4 CEBPB STAT2_30m HDAC2 PU1 NRF1 GATA1 FOSL ATF3 CTCF BRG1 NFE2 MEF2A ETS1 BCLAF MAFK MXI1 YY1 STAT2_6h TFIIIC NR4A1 P300 TAF7 SIN3A JUND SIRT6 GTF2F1 SRF TAF1 BCL3 INI1 STAT1_30m ZNF263 SMC3 THAP1 CTCFL STAT1_6h NELFE SETDB1 SPT5 RPC155 ZBTB33 RAD21 NRSF TR4 BDP1 POL3 ZNF274 BRF1 KAP1 BRF2 XRCC4 14,404 21,313 20,609 23,586 14,496 9,862 1,623 18,815 20,895 6,932 13,693 6,402 17,951 29,410 15,401 9,229 16,358 18,480 9,860 5,576 19,094 9,025 24,841 8,031 3,397 2,475 5,025 10,662 10,746 44,168 2,514 8,831 25,479 3,328 3,182 11,393 939 46,476 11,209 3,477 10,209 2,607 6,616 17,914 3,020 5,250 2,174 10,004 5,514 2,969 4,536 2,701 945 1,794 885 2,005 4,126 3,924 8,061 1,057 8,128 23,337 1,606 8,572 1,245 1,136 8,379 1,839 2,075 4,530 17,401 5,715 612 520 563 794 317 12,314 67 201 6,001 6,413 6,674 5,775 3,516 1,589 517 4,691 8,724 1,206 5,047 2,011 7,935 4,844 9,013 2,372 7,309 10,485 5,618 2,247 8,480 5,927 15,970 3,793 332 455 1,213 3,330 5,081 11,542 1,593 4,751 8,488 478 1,672 6,788 78 6,067 5,408 2,223 4,389 1,157 2,758 6,545 517 791 1,153 3,175 1,709 1,040 1,254 320 256 1,230 90 666 580 493 3,796 605 1,324 2,531 206 1,224 519 46 669 197 623 678 1,855 691 44 84 46 12 26 437 4 3 5,969 6,384 6,617 5,706 3,494 1,587 517 4,655 8,639 1,205 4,985 2,002 7,866 4,819 8,890 2,340 7,291 10,399 5,473 2,228 8,427 5,876 15,864 3,773 330 452 1,212 3,308 5,039 11,470 1,580 4,700 8,424 478 1,665 6,742 78 6,031 5,363 2,213 4,337 1,153 2,712 6,532 517 791 1,149 3,164 1,685 1,038 1,237 318 256 1,227 90 666 573 492 3,762 602 1,322 2,531 204 1,216 517 46 669 197 622 674 1,854 691 44 84 46 12 26 437 4 3 76 82 85 73 45 20 7 59 110 15 64 26 100 62 114 30 93 133 70 28 108 75 203 48 4 6 15 42 64 146 20 60 108 6 21 86 1 77 68 28 55 15 35 83 7 10 15 40 22 13 16 4 3 16 1 9 7 6 48 8 17 32 3 16 7 1 9 3 8 9 24 9 1 1 1 0 0 6 0 0 1,246 869 619 587 471 384 242 503 649 302 478 321 539 431 562 296 468 526 335 204 386 314 545 235 81 88 128 197 240 387 128 219 302 74 120 246 35 224 196 118 170 82 127 212 55 66 78 127 85 63 65 34 31 64 20 39 36 32 106 33 48 73 17 43 26 9 29 15 25 25 49 25 3 4 2 1 1 7 0 0 39 27 19 18 15 12 8 16 20 9 15 10 17 13 18 9 15 16 10 6 12 10 17 7 3 3 4 6 8 12 4 7 9 2 4 8 1 7 6 4 5 3 4 7 2 2 2 4 3 2 2 1 1 2 1 1 1 1 3 1 2 2 1 1 1 0 1 0 1 1 2 1 0 0 0 0 0 0 0 0 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 <1.0E-300 2.5E-300 1.9E-297 1.9E-290 2.5E-261 4.7E-243 5.4E-225 1.4E-222 4.0E-218 1.9E-193 2.2E-182 6.6E-161 4.4E-123 9.0E-106 3.4E-103 6.2E-100 2.2E-98 2.5E-87 2.5E-77 2.1E-74 6.3E-74 5.6E-70 1.2E-66 2.0E-66 2.0E-60 3.4E-59 7.6E-57 3.1E-55 2.3E-51 1.7E-47 4.6E-45 1.8E-44 5.0E-38 1.1E-37 1.1E-36 4.1E-35 7.1E-35 1.2E-33 1.0E-32 1.4E-32 4.1E-32 1.3E-28 6.6E-26 1.2E-23 4.5E-21 6.8E-21 8.8E-21 1.3E-20 2.7E-19 9.9E-15 1.3E-14 1.4E-13 1.6E-13 6.2E-12 2.8E-10 3.6E-10 1.7E-09 5.0E-09 6.0E-09 6.4E-09 2.2E-08 5.0E-08 7.9E-07 3.3E-06 3.4E-06 5.0E-06 1.9E-02 2.3E-02 1.2E-01 1.4E-01 2.8E-01 5.2E-01 1.0E+00 1.0E+00 n= n= 249,997 3193 NF-Y friends Actual Overlap w Hypergeo. # Peaks in # Promoters Expected YB (a) Prob. # Peaks promoters with Factor Overlap w YB RPC155 2075 282 278 53 87 3.11E-08 RAD21 17401 898 883 169 195 0.0002953 XRCC4 201 7 7 1 1 0.3825 TR4 612 241 241 45 78 3.22E-08 ORC2 15401 3522 3404 664 1286 3.18E-199 TFIIIC 10004 2310 2229 436 732 2.52E-71 Pol3 563 65 61 12 15 0.05282 TFIIF 10662 5241 5127 989 1540 1.80E-131 TBP 9933 6068 5945 1145 2295 0.00E+00 SPT5 1839 249 245 47 108 2.32E-21 pS2Pol2 29410 9741 9466 1838 3126 0.00E+00 Pol2 10316 9954 1946 3347 0.00E+00 TFIIB 2475 1445 1424 273 620 9.13E-119 NFE2 3477 380 375 72 122 4.55E-12 ZNF274 794 9 4 2 0 0.4502 ZNF263 8128 1327 1298 250 299 5.84E-07 Ifna6hStat2 2173 341 332 64 88 3.40E-05 Ifna6hStat1 1245 211 208 40 49 0.009042 GATA2 9025 633 621 119 173 3.66E-10 GATA1 3182 225 224 42 55 0.003265 YY1 5250 2534 2510 478 878 1.61E-104 E2F6 20609 9516 9187 1795 3037 0.00E+00 E2F4 9862 7163 7025 1351 2615 0.00E+00 cMYC 13693 6506 6300 1227 2248 0.00E+00 MAX 6402 2534 2500 478 1006 8.17E-172 cJUN 18480 3394 3277 640 1138 8.36E-139 cFOS 14404 2966 2881 560 2279 0.00E+00 JUND 945 308 307 58 124 2.20E-20 ATF3 939 496 495 94 181 3.34E-23 SIRT6 1794 141 141 27 33 0.02241 SETDB1 8379 997 979 188 287 5.13E-19 BRF2 67 7 7 1 2 0.2534 BRF1 317 46 44 9 13 0.02365 BRD4 10746 3203 3139 604 982 1.16E-85 BDP1 520 89 88 17 18 0.08943 GTFs TFs Cofactors NF-Y and friends stay together... ...to make life and death decisions cFos Yes No NF-YB No Yes cJun No No No Yes Yes No Yes No Yes No Yes Yes Yes No Yes Yes Yes Function (p-value <1e-05) Cellular Assembly and Organization None Cell Death, Protein Synthesis, Gene Expression, Cellular Growth and Proliferation, Molecular Transport, Protein Trafficking, 10719 Cell Cycle 4472 Cell Cycle, Gene Expression, DNA Replication, Recombination, Repair, Cellular Assembly and Organization 5980 None 683 None 1155 Cell Cycle, Cellular Function and Maintenance, Cell Death 2884 6345 ChIP-Seq Tag Distribution 14 cFos cJun NFYB RefSeq Normalized Tag Count 12 10 8 cFos cJun NFYA NFYB Input_Struhl 6 4 2 0 -500 -250 0 250 Distance from cFos peak summit (bps) 500 5’ The amazing precision of ChIP-Seq -1 A T 1 -2 A T 2 -3 G C 3 -4 A T 4 Gln 97 Arg 93 L2 (C) Arg 94 Thr 95 Lys 75 L1 (B) -5 G C 5 a2 (B) Lys 78 Ala 77 -6 6 A T L1 (B) Ile 76 Lys 75 -7 G C 7 a2 (B) Lys 81 Gly 287 -8 Met 279 A2 C 8 G C 9 Arg 288 -9 His 275 Phe 289 Arg 283 His 271 A1A2-linker G Gly 286 -10 T A -11 T A Ser 291 10 Leu 270 Arg 281 Pro 58 Ile 59 Ala 60 a1 (B) 11 His 277 -12 A T 12 -13 G C 13 Asn 61 Arg 64 A2 Arg 274 -14 A T 14 -15 G C 15 -16 G C 16 Ser 273 His 271 A1A2-linker Gln 53 Lys 50 Arg 47 a1 (C) Ala 46 Leu 45 Met 60 Lys 53 Lys 49 L1 (C) a1 (C) -17 C G 17 -18 T A 18 -19 C G 19 -20 G C 20 -21 A T 21 -22 G C 22 Pro 44 Ile 61 Ser 62 Ala 63 -23 C G 23 -24 T A 24 Lys 109 -25 5’ A T 25 L2 (B) Where do the friends sit at the table? ? CCAAT ? E2F E box AP1 TBP We can tell Reconstructing promoters architecures 10 E box AP1 50 CCAAT E2F TBP Protein transfections of TAT-NF-YA in vivo. Domashenko, Blood, 2010. Progenitor cells Pancreatic cell Endoderm Hepatocyte ES cell Myoblast Mesoderm Hematopoietic cells HSCs Totipotent cell Ectoderm Neuron Epithelial cell Pluristratified VINCULIN TAT-NF-YAs NF-YAl NF-YAs SOX2 NANOG Fold enrichment KLF5 5 4 3 NT 2 1 w/oLIF w/oLIF+TAT w/oLIF+TAT-YAs 0 PROMOTERS WITH CCAAT PSFM SCORE>0.8 % ChIP-Seq data NF-YA promoters 21747 5493 25.26 2400 GENOME PROMOTERS BACKGROUND TFs PROMOTERS ( -500 +100) PROMOTERS WITH CCAAT PSFM SCORE>0.8 E2F1 6102 2183 35.78 5.11E-106 1472 0 NANOG 343 163 47.52 9.61E-020 144 7.25178E-50 1.25421E-25 P-value P-value KLF4 2966 900 30.34 6.52E-012 505 SOX2 178 78 43.82 2.07E-008 41 2.11146E-06 ESRRB 1240 383 30.89 1.76E-006 169 0.000491226 STAT3 320 101 31.56 4.35E-003 64 8.86847E-07 OCT4 660 193 29.24 8.07E-003 131 6.53472E-12 CTCF 1308 301 23.01 9.72E-001 228 2.80016E-13 TFBs analysis on Nanog core promoters TF NAME MATRIX ID P-VALUE TF NAME MATRIX ID P-VALUE NFYA MA0060.1 4.86E-27 GABPA MA0062.2 1.83E-234 MIZF MA0131.1 1.92E-17 ELK4 MA0076.1 2.94E-220 ELK4 MA0076.1 2.36E-16 ELK1 MA0028.1 5.17E-168 GABPA MA0062.2 1.18E-14 E2F1 MA0024.1 9.10E-156 ELK1 MA0028.1 1.50E-13 MIZF MA0131.1 2.36E-152 E2F1 MA0024.1 1.22E-11 TFAP2A MA0003.1 7.63E-111 HIF1A::ARNT MA0259.1 5.98192 NFYA MA0060.1 3.65E-108 Mouse Mouse promoters Nanog peaks Ranking positions third Human promoters Nanog peaks Ranking positions first Human 82.2 60 Fold enrichment ChIP:NF-YB Nanog peaks de novo discovery analysis 89.3 50 40 30 20 10 ChIP:NANOG Fold enrichment 0 10 NF-YB FAM33A SOX2 NF-YA NF-YC HMGB2 CDK2 STARD4 STIL OTX2 LEFTY NF-YAs NF-YAsm29 8 6 4 2 0 HMGB2 CDK2 STARD4 ChIP-Seq: NANOG NF-YB - FAM33A + SOX2 + NF-YA NF-YC + + + + STIL + OTX2 + LEFTY + ChIP-Seq: NF-YA + + - + + - + + + - A growing network of TFs in ESC. NF-YC 37 NF-YB NF-YA Short KLF4 SALL4 MYC STAT3 OCT4 SOX2 NANOG Past Post-Docs Khalid Zemzoumi Alberto Di Silvio (Axxam I) Fabienne Cocchiarella (UniMo) Marià Pitarque Martì Anna Testa Nicoletta Cordani (HSR, I) Silvia Pozzi (Reg Emilia) Alessandra Viganò (U. Basel, CH) PhDs Maria Carla Motta (U. Manchester UK) Patricia Lievens Chiara Liberati (Axxam, I) Giuseppina Caretti (UniMi I) Mattia Frontini (MRC UK) Carol Imbriano (UniMo I) Barbara Testoni (CNRS F) Claudia Forni (Farmigea I) Giacomo Donati (MRC UK) Michele Ceribelli (NIH USA) Daniele Merico (U. Toronto CA) Andrea Fossati (UniMi I) Marianna Bellorini Chiara Vecchi (UniMo I) Valentina Salsi (UniMo I) Giulia Petrovich (U. Edimburgh UK) DSBB U. Milano Present Serena Borrelli Raffaella Gatta Diletta Dolfini Elena Martynova Mario Minuzzo Nerina Gnesutta Mariangela Lorenzo Federico Zambelli Giulio Pavesi Marco Nardini Martino Bolognesi Collaborators C Imbriano L Tora C Romier C Castagnoli G Melino A Terrinoni E Candi D Aberdam GP Dotto E Berti M d’Incalci D. Hochhauser J. Fleming/K. Struhl Active Motif (USA) U Modena (I) IGBMC (F) IGBMC (F) B.Cute Torino (I) MRC Leicester (I) IDI (I) U. Roma (I) INSERM-Nice (F) U. Lausanne (CH) U. Mi-Bicocca (I) Ist Mario Negri (I) UCL (UK) Harvard (USA)