Supplemental Material to

Landes Bioscience

www.landesbioscience.com

Supplemental Material to: Holger Heyn, Sebastian Moran and Manel Esteller Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner Syndrome Epigenetics 2013; 8(1) http://dx.doi.org/10.4161/epi.23366 http://www.landesbioscience.com/journals/epigenetics/article/23366

Supplementary table 1: 144 consistent dmCpG sites in AG07896/AG11385 and natural aged samples. TargetID cg09668627 cg02136596 cg07312051 cg17278062 cg00352106 cg25369262 cg07107453 cg21863110 cg25216580 cg00791854 cg17166812 cg17936236 cg21110645 cg01012879 cg13973086 cg09074113 cg06108254 cg22880770 cg11916609 cg20608990 cg15335768 cg04731861 cg04621728 cg16967583 cg08003402 cg12934382 cg02331649 cg13679804 cg20037507 cg18746336 cg00355829 cg15467503 cg00076653 cg26689483 cg19676182 cg09168222 cg08736088 cg24894783 cg09017434 cg03873281 cg17781669 cg02727079 cg14417687 cg17091577 cg00244776 cg04665604 cg12988118 cg22986222 cg26069291 cg22774605 cg24690314 cg12419863 cg09595020 cg10822172

Chr. 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 4 4 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 7 7

Position 1371844 1384930 15656086 17732728 39864197 46649132 79114976 116380417 120173989 154392070 161169574 167520305 207815933 244613363 469105 20870087 72830705 97166341 102927488 202097607 218268053 219085781 234934131 241807859 15311021 51741135 52926322 59734950 62363248 128216122 128326679 1727234 15341878 17513197 24981695 89299733 147866520 10577031 16179660 131608955 149868359 17986167 30042260 30854233 30883192 31696852 31744524 32095276 42716310 47247047 144018564 144263450 2654120 28338757

Gene symbol VWA1 ATAD3C FHAD1

Location Body Promoter Body

CpG context Island shore

GDF7 EXOC6B NEURL3 IL1RL1 CASP8 DIRC3 ARPC2

Island shore Body Body Promoter 3'UTR Island Promoter Body Promoter;Promoter Island shelf Body Island shelf Island shelf Body Island shore Island shore Body Island Body Body Island Promoter Promoter Body Body Island shelf

AGXT SH3BP5 GRM2 TMEM110

Promoter Body Promoter Body

MACF1 TSPAN1 IFI44 NHLH2 ZNF697 IL6R NDUFS2;ADAMTS4 CREG1 ADSS

TACC3 C1QTNF7 QDPR CCDC149 HERC6 TTC29 ANKRD33B MARCH11 PDLIM4

Body Body Body Promoter Promoter Promoter Body Promoter 3'UTR

KIF13A RNF39 DDR1 VARS2 DDAH2 C6orf27 ATF6B

Body Body Promoter Body Body Body Body

TNFRSF21 PHACTR2 PLAGL1 IQCE CREB5

Body Body Body 3'UTR Promoter

Island

Island shore Island Island shore Island shelf Island shore Island shore Island shore Island Island shore Island shelf Island shore Island shore Island shore Island shore Island Island shelf Island shore

cg15626881 cg02060682 cg19759064 cg15893346 cg09748749 cg14667235 cg14823389 cg11961845 cg19073171 cg23109344 cg26122129 cg19496364 cg11057205 cg13707760 cg10394788 cg26581729 cg24381155 cg23901918 cg01213599 cg22891191 cg05895618 cg08214808 cg04465784 cg04265051 cg11155924 cg00242341 cg07101980 cg01314044 cg14242895 cg16983588 cg12409074 cg08799922 cg27117982 cg27651238 cg16726039 cg09337121 cg07176842 cg25576997 cg18186343 cg03039990 cg18580117 cg06687489 cg24665265 cg11442608 cg09763373 cg05638439 cg09308553 cg03746976 cg05969150 cg11801411 cg03613822 cg01538166 cg13895343 cg04193015 cg20629183 cg19057899 cg22892904 cg19761273 cg24914483

7 7 7 7 7 7 7 7 7 8 8 8 8 9 9 9 10 10 10 10 11 11 11 11 11 11 11 11 11 11 11 12 12 12 12 14 14 14 14 14 15 15 15 15 16 16 16 16 16 17 17 17 17 17 17 17 17 17 18

33923464 36190724 56160687 65447565 65540429 76026648 101398152 129008179 154793806 496440 30241119 94551463 134588243 95986383 124360547 139939792 103289745 105420747 126704259 129706234 19222395 45922166 67976953 68079686 70449258 72447419 77780019 94246036 118393450 129793108 129870648 7245030 16500077 52644264 133413162 23769999 43972223 56257750 101317620 101317622 42787236 52587077 70852115 81456832 596899 711235 56763573 58035805 72882495 1628727 7115140 17743987 26708773 35596680 41985830 47093955 77751089 80232096 2653997

Island shore PHKG1 GUSB ASL ZP3;SRCRB4D

Promoter Promoter Promoter Promoter;Body

Island shore Island shore Island shore

AHCYL2 PAXIP1;LOC202781 C8orf42 RBPMS

Promoter Body;Promoter Promoter Promoter

Island shore Island shore Island shore

WNK2 DAB2IP NPDC1 BTRC SH3PXD2A CTBP2 PTPRE CSRP3 MAPK8IP1 SUV420H1 LRP5 SHANK2 ARAP1 NDUFC2

Body Body Body Body Body Body Promoter Promoter Body Promoter Promoter Body Promoter 3'UTR

MLL PRDM10 PRDM10 C1R MGST1

3'UTR Body Promoter Promoter Promoter

Island shelf Island Island Island Island Island Island shelf Island shore

Island shore

Island shore

PPP1R3E

Body

Island Island Island shore

C14orf34 MIR770;MEG3 MIR770;MEG3 SNAP23 MYO5C

Body Promoter;Body Promoter;Body Promoter Body

Island shelf Island shore

SOLH WDR90 NUP93 C16orf57 ZFHX3 WDR81 DLG4

Body Body Promoter Body Body Body Body

SARM1 ACACA MPP2 IGF2BP1 CBX2 CSNK1D

Body Body Promoter Body Promoter Promoter

Island shore Island Island shore Island shore Island Island shelf Island Island Island shore Island shore Island shore Island shore Island shore

cg20916427 cg24304425 cg26316885 cg18745507 cg11453058 cg08196968 cg25734726 cg22891070 cg16672562 cg16617301 cg23314866 cg00822241 cg05925291 cg24263062 cg24165121 cg01260366 cg19811118 cg00340958 cg06260709 cg11074047 cg11853697 cg11726250 cg22138735 cg24753998 cg16057826 cg26390598 cg00546897 cg13762691 cg06942979 cg01264106 cg19582200

18 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 20 20 20 20 21 21 21 21 22 22 22 22

44627440 840985 10407317 10415557 14064176 38746749 40948296 46801642 46801672 46999109 48016020 49201468 54617809 2730191 23398291 32307172 43160245 48328658 48626621 50157455 60510235 61924405 62679713 30452964 36041334 41032396 45232232 17956560 31501382 38071602 43602629

KATNAL2 PRTN3 ICAM5 ZGLP1 PODNL1 PPP1R14A SERTAD3 HIF3A HIF3A PNMAL2 NAPA FUT2 PRPF31;TFPT EBF4 NAPB PXMP4 PKIG B4GALT5

3'UTR Promoter 3'UTR 3'UTR Promoter Body Promoter Body Promoter Promoter Body Promoter Promoter;Body Body Body Body Promoter Body

NFATC2 CDH4 COL20A1 SOX18 C21orf7 CLIC6 B3GALT5 LOC284837 CECR2 SELM LGALS1 SCUBE1

Body Body Promoter Body Promoter Promoter Promoter Body Promoter Body Promoter Body

Island shelf Island Island shore Island Island shore Island shore Island shore Island Island shore Island shore Island shore Island Island shelf Island shore Island shore Island shore Island Island shore Island shore Island shelf Island Island

Island shore Island shore Island shelf

Supplementary table 2: 485 consistent dmCpG sites in AG19911 and natural aged samples. TargetID cg09668627 cg02136596 cg12639453 cg01101873 cg01556552 cg25978218 cg17670191 cg17278062 cg26561681 cg19743168 cg25187161 cg19412669 cg12634306 cg21862529 cg09160123 cg26038582 cg15937073 cg12081325 cg27532171 cg21536783 cg27427318 cg16991569 cg08110488 cg14378231 cg24681307 cg25674286 cg21863110 cg01974375 cg20324858 cg13795986 cg09796170 cg07349663 cg11578532 cg17166812 cg07580762 cg21691116 cg11155784 cg14748380 cg24460126 cg25408950 cg14780255 cg02769705 cg19081101 cg05721773 cg21110645 cg22787719 cg07168232 cg15134583 cg11145399 cg04193160 cg24070990 cg16516400 cg09548403 cg09823288

Chr. 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Position 1371844 1384930 2035780 3269478 10695686 15738732 17026406 17732728 21376633 23544995 29510025 36839270 40098811 41948212 41981735 42384390 42384564 45413279 46952054 59041407 61509328 63142359 82136224 98404032 110526191 112046915 116380417 151298954 154529936 155880507 156548174 160261619 161008127 161169574 161171810 161171819 164572163 179713788 179713828 198290080 201720358 202975059 203156625 207083336 207815933 209570949 209822928 224015075 224034478 228400419 228634724 231177201 232840764 239552128

Gene symbol VWA1 ATAD3C PRKCZ PRDM16

Location Body Promoter Promoter Body

EFHD2 ESPNP

Body Body

EIF4G3

Promoter

SFRS4 STK40 HEYL EDN2 HIVEP3 HIVEP3 HIVEP3 EIF2B3

Promoter Promoter Body Body Body Promoter Promoter Body

TACSTD2

3'UTR

DOCK7

Body

AHCYL1 ADORA3 NHLH2 PI4KB UBE2Q1 RIT1 TTC24 COPA TSTD1 NDUFS2;ADAMTS4 NDUFS2 NDUFS2 PBX1 FAM163A FAM163A NEK7 NAV1 TMEM183B CHI3L1 FAIM3

Promoter Body 3'UTR Promoter Body Body Promoter Body Body Promoter;Promoter Promoter Promoter Body Promoter Promoter 3'UTR Body Promoter Promoter Body

LAMB3 TP53BP2 TP53BP2 OBSCN

Body Body Promoter Body

FAM89A

Promoter

CpG context Island shore Island shelf Island shelf Island shore Island Island shore Island shore Island shore

Island shore Island shore Island shore Island shore Island shore Island shore

Island shore Island Island shore Island shore

Island shore Island shelf Island Island Island Island

Island shore Island shore Island shelf

Island shore Island Island shore Island shore Island shore

cg25683662 cg14830002 cg23230830 cg13973086 cg08398132 cg10646145 cg22495058 cg00484122 cg09074113 cg25101396 cg07858848 cg19275978 cg10855531 cg21852792 cg06108254 cg13391675 cg10203483 cg22880770 cg18145105 cg11916609 cg18145759 cg06021088 cg13700939 cg07143462 cg00760729 cg15739581 cg23808213 cg00883212 cg16164923 cg11608958 cg02577773 cg15335768 cg04731861 cg19701828 cg21566642 cg04621728 cg12157614 cg20513777 cg05758467 cg16967583 cg24371033 cg00085013 cg26792295 cg23715029 cg24595152 cg08033130 cg13719901 cg00906812 cg25021247 cg00664406 cg12934382 cg00303541 cg02331649 cg13679804 cg20037507 cg08173709 cg23333146 cg26108120 cg25338134

1 1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

245771036 247616686 248903100 469105 8557381 9235600 11752373 20579065 20870087 27346296 43087177 60983087 62702472 71678463 72830705 80009927 85646239 97166341 97166422 102927488 109901466 127822551 128166166 157289513 161236088 166626783 166948291 173795201 197504013 207836769 208027870 218268053 219085781 219235515 233284661 234934131 236890427 238533299 240035894 241807859 241807924 14871570 16540091 42201568 43733831 45983597 46608139 47018657 49460162 51740875 51741135 51741280 52926322 59734950 62363248 71103443 71731211 72440793 72940510

KIF26B OR2B11 LOC646627

Body Promoter Promoter

Island shore Island shore

GREB1

Body

Island shore

GDF7 ABHD1

Body Promoter

Island Island shore

PAPOLG

Promoter

Island shore

EXOC6B CTNNA2

Body Body

NEURL3 NEURL3 IL1RL1 SH3RF3 BIN1

Body Body Promoter Body Body

Island shelf

Island shore Island Island

Island Island shelf RBMS1 GALNT3

Body Body

RAPGEF4 CCDC150

Body Promoter

KLF7 DIRC3 ARPC2

Body Body Body

AGAP1

Body

HDAC4 AGXT AGXT FGD5 RFTN1 TRAK1 ABHD5 CXCR6;FYCO1 LRRC2 CCDC12 AMT GRM2 GRM2 GRM2 TMEM110

Body Promoter Promoter Body Promoter Body Body Promoter;Body Promoter Promoter Promoter Promoter Promoter Promoter Body

FOXP1 EIF4E3 RYBP GXYLT2

Body 3'UTR Body Body

Island shore Island shelf Island shelf Island shelf Island

Island shelf Island shelf

Island shore Island shore Island shore Island Island Island

Island shore

cg24969820 cg20267101 cg24954207 cg07593390 cg23466339 cg21552014 cg06800962 cg24474182 cg06168950 cg04481170 cg18123677 cg09696560 cg08179817 cg16760587 cg17173896 cg19676182 cg17688837 cg02170478 cg24918767 cg00382138 cg13056653 cg03476007 cg08736088 cg20818457 cg03065175 cg02140579 cg04399899 cg02525719 cg20639618 cg21633052 cg09017434 cg16578742 cg24539599 cg26811372 cg06677890 cg22594985 cg13954457 cg23476877 cg01287088 cg06033531 cg00549219 cg21010202 cg27095915 cg12662084 cg03089870 cg09248660 cg25583651 cg27342919 cg21809927 cg08222513 cg02049405 cg15978899 cg00244776 cg06151074 cg06928741 cg05667097 cg04665604 cg25264948 cg23526676

3 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5 5 5 5 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6

98497864 113006232 128217091 136714183 138066434 146026497 149096029 151047307 154737057 158445995 167454339 185178617 4335184 17517594 24975754 24981695 25090665 55100995 88297189 110723299 141538969 143768727 147866520 154179401 155661758 159091837 160189254 183728549 183729073 184018637 16179660 35617687 112824920 140772182 149887486 153457958 167956819 176543964 176827392 176980153 177370476 1615843 1624442 17809126 17988960 24969848 29570040 30079256 30079265 30079280 30095265 30882994 30883192 31669888 31691430 31691481 31696852 31734232 31734458

ST3GAL6 BOC;WDR52

Body 3'UTR;3'UTR

IL20RB MRAS

Body Promoter

TM4SF1 MED12L;P2RY13

Promoter Body;Promoter

RARRES1 SERPINI1 MAP3K13

Body Promoter Body

Island shelf Island shore

CLRN2 CCDC149 CCDC149

Body Promoter Promoter

Island shelf

PDGFRA HSD17B11 CFI

Promoter Body Promoter

INPP4B TTC29 TRIM2

Promoter Promoter Body

FAM198B RAPGEF2

Body Promoter

Island shore Island shore

Island shore Island shore

Island shore Island shore Island

C4orf38 MARCH11 SPEF2 MCC PCDHGA4 cluster NDST1

Body Promoter Promoter Promoter Body Promoter

FBLL1

Body

PFN3 FAM193B

Promoter Promoter

GMDS KIF13A KIF13A

Body Body Promoter

GABBR1 TRIM31 TRIM31 TRIM31

3'UTR Body Body Body

VARS2 VARS2 BAT5 C6orf25 C6orf25 DDAH2 C6orf27 C6orf27

Body Body Body Body Body Body Body Body

Island shore Island Island shore Island Island shore Island shore Island shore

Island Island Island Island shore Island shore Island Island Island shore

Island Island shore Island shore Island shore Island Island Island

cg15501231 cg12988118 cg19577206 cg22986222 cg09713850 cg12397463 cg07715777 cg22273555 cg11920449 cg08784966 cg07188523 cg01946401 cg23261343 cg22774605 cg19607845 cg22322277 cg25015371 cg14289461 cg14575356 cg24964103 cg06899237 cg07223240 cg04633141 cg09595020 cg18446336 cg08090407 cg04089901 cg27380915 cg24350771 cg12510708 cg04027736 cg20704555 cg23418219 cg02506717 cg15626881 cg24497732 cg07488141 cg19759064 cg08370546 cg21940640 cg15893346 cg09748749 cg03193328 cg22455527 cg12856114 cg14667235 cg26688582 cg20782117 cg14398883 cg24707573 cg11752788 cg16248756 cg11961845 cg22057675 cg01106572 cg12538435 cg01058360 cg05809437 cg20305578

6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 8 8

31737630 31744524 31866825 32095276 32921791 33128825 33128963 33130034 36645608 37248768 44528793 45296101 45413792 47247047 52934457 75459158 108874950 112575929 130013903 133035379 153353519 170468271 1588319 2654120 2847575 7139271 7557590 12796513 18329602 26193805 27143403 28127748 28338684 28338790 33923464 42278077 47560215 56160687 56160770 56160893 65447565 65540429 65746852 73241878 73242028 76026648 91477554 95865631 101398184 101961796 123438230 127795594 129008179 140103545 150744384 150801757 151442371 1450031 1908301

C6orf27 C6orf27 EHMT2 ATF6B HLA-DMA

Body Body Promoter Body Promoter

Island shore Island shelf Island shore Island shore Island shore Island shore

CDKN1A TBC1D22B

Promoter Body

SUPT3H;RUNX2 RUNX2 TNFRSF21 FBXO9

Promoter;Promoter Body Body Body

LAMA4 ARHGAP18 VNN1 RGS17

Promoter Body Promoter Body

TMEM184A IQCE GNA12

Body 3'UTR Body

COL28A1

Body

NFE2L3 HOXA2 JAZF1 CREB5 CREB5

Body Promoter Body Promoter Promoter

Island shore Island

GLI3 TNS3 PHKG1 PHKG1 PHKG1 GUSB ASL TPST1

Promoter Promoter Promoter Promoter Promoter Promoter Promoter Body

Island shore

ZP3;SRCRB4D

Promoter;Body

SLC25A13

Body

SH2B2

Body

AHCYL2 RAB19 ACCN3ABCB8 AGAP3 PRKAG2 DLGAP2

Promoter Promoter Promoter Body Body Promoter

Island shelf Island shelf Island shore

Island shore

Island shore Island shore Island shelf Island shelf Island shore

Island

Island shore

cg12036735 cg26122129 cg10327067 cg19695041 cg01632240 cg17292662 cg19678968 cg19496364 cg11057205 cg24107665 cg07013148 cg07158339 cg16509045 cg14438325 cg10394788 cg17930194 cg00300627 cg13754665 cg14243817 cg14126392 cg21120249 cg13579295 cg13274149 cg03383434 cg13811936 cg09877009 cg15835339 cg01283625 cg17078883 cg19307545 cg12479507 cg20283498 cg18786171 cg05552874 cg07225966 cg15903032 cg24381155 cg05042708 cg23901918 cg05329352 cg01213599 cg14479798 cg22891191 cg07986469 cg15281331 cg24427660 cg15232290 cg20973931 cg05586607 cg17611235 cg03306615 cg13059136 cg21052766 cg13837679 cg13809236 cg08214808 cg00187686 cg14328641 cg03559942

8 8 8 8 8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 11 11 11 11 11 11 11 11 11 11 11 11 11 11

20169916 30241119 37549202 38615330 42009223 54758936 59185164 94551463 134588243 144372932 146233339 71650237 77502963 124023910 124360547 124982834 132646360 136654631 138876879 138985942 139921971 140069745 140175393 140318662 141017001 6605133 10828105 13568099 28759936 35028929 57390047 73387917 75935758 91153143 94820376 101297605 103289745 105212813 105420747 112838983 126704259 129533998 129706234 129795003 133879497 818892 1785683 1785695 1965447 1991188 2292890 2986541 20134289 44329915 45908036 45922166 59634218 59822727 62521055

RBPMS

Promoter

Island shore Island shelf Island shore Island shore Island shelf

TACC1 AP3M2

Promoter Promoter

ZNF696

Promoter

Island shelf Island

FXN TRPM6

Promoter Promoter

Island shore Island shore

DAB2IP LHX6

Body Body

Island Island Island shore

VAV2

Body

NACC2 C9orf139;ABCA2 ANAPC2 C9orf167 EXD3;NOXA1 CACNA1B PRKCQ SFTA1P

Promoter Promoter;Body Body 3'UTR Promoter;Body 3'UTR Promoter Body

Island shelf Island Island shore Island shore Island Island Island shelf

Island shelf PARD3

Body

CDH23 ADK IFIT1 CYP26C1

Body Body Body Promoter

BTRC CALHM2 SH3PXD2A ADRA2A CTBP2

Body Promoter Body Promoter Body

PTPRE PTPRE

Promoter Promoter

PNPLA2 CTSD;HCCA2 CTSD;HCCA2

Promoter Promoter;Promoter Promoter;Promoter

ASCL2 SNORA54;NAP1L4 NAV2 ALX4 MAPK8IP1 MAPK8IP1 TCN1 MS4A3 ZBTB3

Promoter Promoter;Body Body Body Body Body Promoter Promoter Body

Island shore Island shore Island Island Island shore Island Island Island shore Island Island shore Island shore Island shore Island shore Island shelf Island Island

Island shore Island shore Island

Island shore

cg20705781 cg06518251 cg04465784 cg04265051 cg11194613 cg11155924 cg10010533 cg02175321 cg22033281 cg03962678 cg26878709 cg10647465 cg16983588 cg12409074 cg01692842 cg16728539 cg18173184 cg05060607 cg22916586 cg11905611 cg22221831 cg17817168 cg13594630 cg00832457 cg05190176 cg27651238 cg11848173 cg00293940 cg12707346 cg20922821 cg26537335 cg14829814 cg06196801 cg07529210 cg23060047 cg13315047 cg16726039 cg11845168 cg05830425 cg15234627 cg03278564 cg12861503 cg18535410 cg09337121 cg07176842 cg25576997 cg24025255 cg12848614 cg06992688 cg01022345 cg05873568 cg02392882 cg04870120 cg15175581 cg09347959 cg07047589 cg18580117 cg05061769 cg24665265

11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 13 13 13 13 13 13 14 14 14 14 14 14 14 14 15 15 15 15 15 15 15 15

67070238 67776030 67976953 68079686 70268728 70449258 82445170 103930844 111325754 118398094 120197138 126582242 129793108 129870648 134126364 2451169 6718378 8211391 12686957 14720974 15039397 22486454 32108895 32287236 48290002 52644264 56121015 60044871 64960957 94070578 105136339 108294894 121164025 122019110 130819504 131261143 133413162 21457096 21654356 33837178 49200201 52734071 113793268 23769999 43972223 56257750 69617774 70193496 94491958 101317819 105155145 29031879 32999748 33360262 33360271 40642998 42787236 59700360 70852115

SSH3 ALDH3B1 SUV420H1 LRP5 CTTN SHANK2 FAM181B PDGFD

Promoter Promoter Promoter Promoter Body Body Promoter Body

Island shore

TTC36 TMEM136 KIRREL3 PRDM10 PRDM10 ACAD8 CACNA1C

Promoter Promoter Body Body Promoter Body Body

Island shelf Island shore

C3AR1 DUSP16 PLBD1 MGP ST8SIA1

Body Promoter Promoter Promoter Body

BICD1 VDR

Body Promoter

CD63

Body

CRADD CHST11

Promoter Body

ACADS KDM2B

Body Promoter

XPO4

Body

STARD13

Body

NEK3 F10 PPP1R3E

Promoter Body Body

C14orf34 DCAF5

Body Body

OTUB2 MIR770;MEG3 INF2

Promoter Promoter;Body Promoter

FMN1 FMN1 PHGR1 SNAP23

Promoter Promoter Promoter Promoter

Island shelf Island shore

Island shore

Island shore Island shelf Island shore

Island Island shore Island shelf

Island Island shore

Island shore Island shelf Island shore Island shore Island shelf Island

Island shore Island shore

Island shore Island Island shore Island shore Island shore

Island shelf

cg06856840 cg22812413 cg11442608 cg00525011 cg03363565 cg09408143 cg09763373 cg05638439 cg03829194 cg08190844 cg01215511 cg10111352 cg01157559 cg26843872 cg03042477 cg26929700 cg00921350 cg07280206 cg01932823 cg02078525 cg00401972 cg05976840 cg12654412 cg05969150 cg05915866 cg27466129 cg05832869 cg08550517 cg07082267 cg27586417 cg09001440 cg13049862 cg09940188 cg13916835 cg03433048 cg04970434 cg13377102 cg23365801 cg16513459 cg04658021 cg01538166 cg13895343 cg05388545 cg14834285 cg04193015 cg25416319 cg14377681 cg19003337 cg10035737 cg09983216 cg17179862 cg19057899 cg11440486 cg00901687 cg13896106 cg09096555 cg20322093 cg06245338 cg21868063

15 15 15 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 16 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17 17

80446451 81391742 81456832 122031 474528 524778 596899 711235 875571 2526203 2975552 16082095 29166162 30368792 31472055 49732567 50701499 56554249 57701726 66400395 66400404 67189804 71459826 72882495 73090838 85060822 85240650 85414644 85429035 85577800 87952767 1384170 1686671 2078431 4806453 4838096 7832764 7832909 7832932 8056967 17743987 26708773 29152968 33897374 35596680 37080373 37875709 39780836 42840005 46679715 46681362 47093955 48585216 48585270 72754589 72848358 72931788 74410839 74869001

FAH

Body

RHBDF1 RAB11FIP3 RAB11FIP3 SOLH WDR90

Promoter Promoter Body Body Body

TBC1D24 FLYWCH1 ABCC1

Promoter Promoter Body

TBC1D10B ARMC5 ZNF423 SNX20 BBS2 GPR97 CDH5 CDH5 TRADD

3'UTR Body Body 3'UTR Promoter Promoter Promoter Promoter Body

ZFHX3 ZFHX3 KIAA0513

Body Promoter Promoter

CA5A MYO1C SMYD4 SMG6 CHRNE GP1BA KCNAB3 KCNAB3 KCNAB3 PER1

Body Body Body Body Promoter 3'UTR Promoter Promoter Promoter Promoter

SARM1 CRLF3

Body Promoter

ACACA

Body

ERBB2 KRT17 ADAM11 LOC404266;HOXB6 LOC404266;HOXB6 IGF2BP1 MYCBPAP MYCBPAP SLC9A3R1 GRIN2C OTOP3 UBE2O MGAT5B

Body Promoter Body Body;Promoter Body,Promoter Body Promoter Promoter Body Body Promoter Body Body

Island Island shore Island shore Island Island Island shore

Island shelf Island shelf Island shore Island Island shore

Island shore Island Island shore Island shore Island shore

Island shelf

Island shore Island Island Island Island shore Island Island Island shore Island shelf

Island shelf Island shelf Island shelf Island shore Island shore Island shore Island Island Island shelf

cg00863893 cg24211657 cg12125614 cg19413066 cg13392258 cg17295878 cg25447164 cg06443034 cg09164913 cg19761273 cg21088259 cg24914483 cg18069568 cg06418113 cg20916427 cg23484392 cg12645852 cg24304425 cg10592521 cg27552857 cg24236839 cg05025071 cg14074174 cg10604476 cg27259408 cg18321051 cg04334723 cg25605731 cg25690897 cg11597043 cg17744295 cg22041417 cg16664617 cg23331484 cg08196968 cg14299480 cg11199014 cg22840076 cg22891070 cg16672562 cg23548163 cg16617301 cg24718465 cg11269599 cg22331349 cg22337438 cg04972979 cg24263062 cg05825244 cg25551168 cg24165121 cg09333580 cg01260366 cg18942298 cg19811118 cg06260709 cg11074047 cg11853697 cg03640203

17 17 17 17 17 17 17 17 17 17 17 18 18 18 18 18 18 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 20 20 20 20 20 20 20

76876239 76886742 76886835 76965347 77806190 77924665 78417789 78417973 78963221 80232096 81039990 2653997 43683922 43915901 44627440 66465334 74198774 840985 1560658 4542866 5038822 6887530 7986206 10403908 10427154 12251893 13054427 13054434 15133948 15751612 16178097 16178195 17607007 33718148 38746749 38876666 39798563 41782156 46801642 46801672 46807119 46999109 46999118 52391304 52391350 54327437 749148 2730191 2730488 3065343 23398291 31606541 32307172 42809578 43160245 48626621 50157455 60510235 61145529

TIMP2 TIMP2 TIMP2

Body Body Body

TBC1D16

Body

CSNK1D METRNL

Promoter Body

ATP5A1;HAUS1 RNF165 KATNAL2 CCDC102B

Promoter;Promoter Body 3'UTR Promoter

PRTN3 MEX3D SEMA6B KDM4B EMR1 SNAPC2 ICAM5 FDX1L;RAVER1 ZNF20 CALR CALR CCDC105 CYP4F3 TPM4 TPM4 SLC27A1 SLC7A10 PPP1R14A GGN LRFN1 HNRNPUL1 HIF3A HIF3A HIF3A PNMAL2 PNMAL2 ZNF577 ZNF577 NLRP12 C20orf54 EBF4 EBF4 AVP NAPB BPIL1 PXMP4 JPH2 PKIG

Promoter Body 3'UTR Body Promoter Body Body Promoter;3'UTR Promoter Body Body 3'UTR Promoter Promoter Promoter Body Promoter Body Body Body Body Body Promoter Promoter Promoter Promoter Promoter Promoter Promoter Promoter Body Body Promoter Body Body Body Body Promoter

NFATC2 CDH4 C20orf200

Body Body Promoter

Island Island shore Island shore Island Island shelf Island shore Island shore Island shore Island shore Island shore

Island shelf Island shelf Island shelf Island shore Island shore Island shore Island Island shore Island shore Island shelf Island shelf Island shore Island shore Island shore Island shore Island shore Island Island Island Island shore Island shore Island Island Island Island Island

Island Island Island shore Island shelf Island shore Island shore Island Island shore Island shore Island shore

cg11726250 cg02231404 cg22138735 cg16057826 cg05089897 cg26390598 cg08381918 cg13762691 cg00281467 cg04206417 cg21361322 cg01794929 cg06942979 cg26373518 cg01264106 cg05903330 cg01194538 cg26394940

20 20 20 21 21 21 21 22 22 22 22 22 22 22 22 22 22 22

61924405 62679635 62679713 36041334 38886664 41032396 43221841 17956560 23522460 29601559 31500896 31500940 31501382 31518942 38071602 39542136 43043270 46449461

COL20A1 SOX18 SOX18 CLIC6 DYRK1A B3GALT5 PRDM15 CECR2 BCR EMID1 SELM SELM SELM INPP5J LGALS1 CBX7 CYB5R3 C22orf26;LOC150381

Promoter Body Body Promoter 3'UTR Promoter Body Promoter Promoter Promoter 3'UTR 3'UTR Body Promoter Promoter Body Promoter Body;Promoter

Island shelf Island Island Island

Island Island shore Island Island Island Island shore Island shore Island Island shore Island shore

Supplementary table 3: 78 consistent dmCpG sites between three HGP family members and healthy donors. TargetID cg26840333 cg24875017 cg26561681 cg21171625 cg09502069 cg02464665 cg10075506 cg04131969 cg12302982 cg02975463 cg14608581 cg11067786 cg26682661 cg00653460 cg04556126 cg03885646 cg01797371 cg20507963 cg15398841 cg22985016 cg17774559 cg27586797 cg11937107 cg21133273 cg18117367 cg22764044 cg24892966 cg11574174 cg10923662 cg15708909 cg11387340 cg06119452 cg27084028 cg10186435 cg01579884 cg01953390 cg16562776 cg26162326 cg04671734 cg04122358 cg08242633 cg08781728 cg06226386 cg00225196 cg17816771 cg06730756 cg11284147 cg13979884 cg00748149 cg07044115 cg15996480 cg01612681 cg13308137 cg07745373

Chr. 1 1 1 1 1 1 2 2 2 2 2 2 3 3 3 3 3 4 4 5 5 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 7 8 8 8 8 8 8 8 8 8 9 9 10 10 11 11 11

Position 4711419 17026258 21376633 38022607 224372558 231156359 1817351 33951647 39471028 45178953 70122240 74780467 38561466 101406220 147106561 156273458 195578240 13541863 74847761 497397 1879698 13664584 72511061 72526964 140213783 178986830 27526023 31237034 32064258 32487314 166970727 169621662 6836436 22492438 37004390 44105764 56606401 75957061 2591207 2591265 2591411 21882587 22500449 37556863 91099036 142198993 144437914 74061171 128171030 123100181 133484592 2322386 47528955 58941415

Gene symbol

Location

CpG context Island shelf Island

ESPNP EIF4G3 DNALI1 DEGS1 MIR1182;FAM89A MYT1L MYADML

Body Promoter Promoter Body Promoter;Body Body Body

SNRNP27 LOXL3;DOK1 EXOG RPL24 ZIC4 SSR3

Body Promoter;Promoter Body Promoter 3'UTR Promoter

PF4 SLC9A3 IRX4

Promoter Body Body

Island shore Island Island shore Island

PCDHA cluster RUFY1

Promoter Promoter

Island shore Island shore Island shore Island

HLA-C TNXB HLA-DRB5 RPS6KA2 THBS2 RSPH10B MGC87042 ELMO1 PGAM2

Body Body Body Body Body Body Body Promoter Promoter

Island shore Island Island shelf

YWHAG

3'UTR

Island shore

NPM2 FLJ14107;BIN3

Promoter Promoter;Body

Island

Island Island shore

Island shore Island Island shore Island shore Island shore Island shore Island shore

Island shore

Island shore

Island shore DENND3

Body Island shelf Island shore Island

C11orf21;TSPAN32 CUGBP1 DTX4

Body;Promoter Promoter Body

Island shore

cg08923614 cg12974393 cg26654770 cg08143343 cg08254200 cg23302649 cg06394109 cg01412970 cg03554335 cg02243479 cg07488417 cg17121205 cg07557707 cg21235746 cg03287299 cg20295248 cg16763089 cg10831901 cg11577716 cg16334795 cg00944631 cg13405775 cg17988310 cg05418105

11 11 12 12 12 14 16 17 17 17 18 19 19 20 20 20 20 20 20 21 22 22 22 22

74303294 107779099 740100 85307152 113229804 29243690 1152511 17109239 62075151 78859959 45274578 44009353 58549711 5485144 5485245 5485270 5485284 5485294 20258001 42538894 20464947 32599648 40355732 50981406

POLD3

Promoter

NINJ2 SLC6A15 RPH3A C14orf23

Body Promoter Promoter Body

PLD6 C17orf72 RPTOR

Promoter Promoter Body

PHLDB3 ZSCAN1 LOC149837 LOC149837 LOC149837 LOC149837 LOC149837 C20orf26 BACE2

Promoter Body Body Promoter Promoter Promoter Promoter Body Promoter

RFPL2 GRAP2

Promoter Body

Island shore

Island shore Island Island Island Island shelf Island shore Island shore Island

Island shore Island shelf

Island shore