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Fig. 1
CpG Islands
Promoters
Fig. 1
New
Fig. 2
Fig2.MethDist.pdf
Fig. 2
New
http://dldccweb.brc.bcm.edu/lilab/deqiangs/data/GO/AGE3/mis2/Po
olTwo/EPP/RegAllDimerCvd/Histogram/epigenomeDeta
ils.DimerWiKoDiff.txt.pdf
Fig. 3
a
c
CpG methylation of basal genes in WT
CpG methylation of down-regulated genes in KO
b
CpG methylation of basal genes in KO
d
CpG methylation of up-regulated genes in KO
Fig. 3
NEW
a
c
CpG methylation of basal genes in WT
CpG methylation of down-regulated genes in KO
b
CpG methylation of basal genes in KO
d
CpG methylation of up-regulated genes in KO
Fig. 4
DMR associated genes
403 Dmnt3a-KO hypo-methylated genes
Oncomine Concepts
Overlapped Genes adjusted p-value
Cancer Gene Census - all causal cancer genes
20
1.2E-07
Acute Myeloid Leukemia - CBFB-MYH11 Gene Fusion - Top 5% Over-expressed (Valk Leukemia)
37
2.0E-05
Acute Lymphoblastic Leukemia - BCR-ABL1 Gene Fusion - Top 1% Over-expressed (Ross
Leukemia)
13
6.0E-03
Acute Myeloid Leukemia vs. Normal - Top 1% Over-expressed (Haferlach Leukemia)
13
7.0E-03
KEGG Pathways
mmu05200:Pathways in cancer
20
8.2E-03
mmu04810:Regulation of actin cytoskeleton
16
1.5E-02
420 Dmnt3a-KO hyper-methylered genes
Oncomine Concepts
Cancer Type: Leukemia - Top 5% Under-expressed (Wooster CellLine)
Cancer Type: Leukemia - Top 5% Under-expressed (Ramaswamy Multi-cancer)
Hypermethylated genes in cancer
KEGG Pathways
mmu04916:Melanogenesis
36
21
12
7.0E-03
1.5E-02
2.5E-02
9
1.5E-02
Fig. 4
New
DMR associated genes
439 Dmnt3a-KO hypo-methylated genes
Oncomine Concepts
Cancer Gene Census - all causal cancer genes
Acute Myeloid Leukemia - CBFB-MYH11 Gene Fusion - Top 10% Over-expressed
Acute Lymphoblastic Leukemia - BCR-ABL1 Gene Fusion - Top 1% Over-expressed
B-Cell Acute Lymphoblastic Leukemia - Top 5% Over-expressed (Haferlach Leukemia)
KEGG Pathways
mmu05200:Pathways in cancer
mmu04810:Regulation of actin cytoskeleton
550 Dmnt3a-KO hyper-methylered genes
Oncomine Concepts
Cancer Type: Leukemia - Top 10% Under-expressed (Wooster CellLine)
Cancer Type: Leukemia - Top 5% Under-expressed (Ramaswamy Multi-cancer)
Hypermethylated genes in cancer
KEGG Pathways
mmu04916:Melanogenesis
Overlapped Genes adjusted p-value
20
8.9E-07
59
4.5E-04
14
7.0E-03
52
1.7E-06
21
16
2.0E-02
6.8E-02
86
24
24
2.0E-05
3.4E-02
2.9E-08
9
5.0E-02
http://www.sanger.ac.uk/genetics/CGP/Census/
Fig. 4
AFF3
ARHGEF12
BCL3
BRCA2
CCND1
COL1A1
EPAS1
ETV6
FNBP1
FOXO4
HIP1
MECOM
MEN1
MSI2
PDGFRB
PRDM16
PTCH1
RBM15
RUNX1
WAS
20 causal cancer genes are associated with Dmnt3a-KO hypo DMR
AF4/FMR2 family, member 3
Rho guanine nucleotide exchange factor (GEF) 12
B-cell CLL/lymphoma 3
breast cancer 2, early onset
cyclin D1
collagen, type I, alpha 1
endothelial PAS domain protein 1
ets variant 6
formin binding protein 1
forkhead box O4
huntingtin interacting protein 1
MDS1 and EVI1 complex locus
multiple endocrine neoplasia I
musashi homolog 2 (Drosophila)
platelet-derived growth factor receptor, beta polypeptide
PR domain containing 16
patched homolog 1 (Drosophila)
RNA binding motif protein 15
runt-related transcription factor 1
Wiskott-Aldrich syndrome (eczema-thrombocytopenia)
APBA1
CDH13
CDKN1C
GNAS
MAGEL2
MEG3
MYOD1
NNAT
PEG10
PPAT
SEZ6L
SLC22A3
Hatada et al. Genome-wide profiling of promoter methylation in human. Oncogene (2006)
vol. 25 (21) pp. 3059-64
12 Hypermethylated genes in cancer are associated with Dmnt3a-KO hyper DMR
amyloid beta (A4) precursor protein-binding, family A, member 1
cadherin 13, H-cadherin (heart)
cyclin-dependent kinase inhibitor 1C (p57, Kip2)
GNAS complex locus
MAGE-like 2
maternally expressed 3 (non-protein coding)
myogenic differentiation 1
neuronatin
paternally expressed 10
phosphoribosyl pyrophosphate amidotransferase
seizure related 6 homolog (mouse)-like
solute carrier family 22 (extraneuronal monoamine transporter), member 3
http://www.sanger.ac.uk/genetics/CGP/Census/
Fig. 4
New
AFF3
ARHGEF12
BCL3
BRCA2
CCND1
COL1A1
EPAS1
ETV6
FNBP1
FOXO4
HIP1
MECOM
MEN1
MSI2
PDGFRB
PRDM16
PTCH1
RBM15
RUNX1
WAS
20 causal cancer genes are associated with Dmnt3a-KO hypo DMR
AF4/FMR2 family, member 3
Rho guanine nucleotide exchange factor (GEF) 12
B-cell CLL/lymphoma 3
breast cancer 2, early onset
cyclin D1
collagen, type I, alpha 1
endothelial PAS domain protein 1
ets variant 6
formin binding protein 1
forkhead box O4
huntingtin interacting protein 1
MDS1 and EVI1 complex locus
multiple endocrine neoplasia I
musashi homolog 2 (Drosophila)
platelet-derived growth factor receptor, beta polypeptide
PR domain containing 16
patched homolog 1 (Drosophila)
RNA binding motif protein 15
runt-related transcription factor 1
Wiskott-Aldrich syndrome (eczema-thrombocytopenia)
Hatada et al. Genome-wide profiling of promoter methylation in human. Oncogene (2006)
vol. 25 (21) pp. 3059-64
12 Hypermethylated genes in cancer are associated with Dmnt3a-KO hyper DMR
APBA1
APBA2
CDH13
CDKN1C
GABRA5
GABRB3
GABRG3
GNAS
GNMT
GRB10
HLA-F
LOX
amyloid beta (A4) precursor protein-binding, family A, member 1
amyloid beta (A4) precursor protein-binding, family A, member 2
cadherin 13, H-cadherin (heart)
cyclin-dependent kinase inhibitor 1C (p57, Kip2)
gamma-aminobutyric acid (GABA) A receptor, alpha 5
gamma-aminobutyric acid (GABA) A receptor, beta 3
gamma-aminobutyric acid (GABA) A receptor, gamma 3
GNAS complex locus
glycine N-methyltransferase
growth factor receptor-bound protein 10
major histocompatibility complex, class I, F
lysyl oxidase
Microarray
data
No overlap with hyper
methylated genes
detected through
RRBS hyper DMR
Association with public TF ChIP-seq/chip data
Down in 3AKO
TF-PubmedID
E2F4-17652178
MYC-19030024
E2F1-18555785
POU5F1-18358816
POU5F1-18692474
POU5F1-18347094
SOX2-18692474
CREM-20920259
ERG-20887958
MYC-18358816
KLF4-18358816
NR0B1-18358816
TRIM28-19339689
PPARG-20887899
MYCN-18555785
TCF3-18347094
NACC1-18358816
RUNX1-20887958
NANOG-18358816
ZFX-18555785
ZFP281-18757296
NANOG-18347094
MYC-18555785
SOX2-18358816
KLF4-18555785
HNF4A-19822575
KLF4-19030024
MYCN-21190229
EOMES-20176728
SOX2-20726797
STAT4-19710469
NANOG-18692474
GFI1B-20887958
CNOT3-19339689
SETDB1-19884257
MYC-19079543
Target/Input
39
67
65
26
60
41
52
71
39
52
34
33
45
49
37
36
20
24
25
43
32
31
24
19
35
62
26
13
28
35
29
38
28
25
32
24
Targets/Databas
e
1002
3868
4172
753
4233
2109
3319
5776
1969
3413
1700
1691
3072
3565
2261
2221
769
1120
1232
3249
2004
1908
1200
785
2444
6083
1502
373
1744
2564
1939
3052
1871
1547
2353
1458
Up in 3A KO
p-Value
2.60E-22
2.49E-19
2.08E-16
6.71E-14
3.05E-13
3.57E-13
4.92E-13
8.00E-13
8.59E-13
1.42E-12
2.48E-11
9.50E-11
2.48E-10
2.73E-10
7.48E-10
1.70E-09
7.06E-09
8.01E-09
1.09E-08
1.38E-08
2.24E-08
2.61E-08
2.88E-08
5.17E-08
6.37E-08
7.51E-08
1.21E-07
1.42E-07
1.72E-07
1.99E-07
4.28E-07
5.34E-07
6.86E-07
7.51E-07
7.87E-07
9.30E-07
TF-PubmedID
Target/Input
SOX2-20726797
58
HNF4A-19822575
90
TCFAP2C-20176728
56
PPARG-20887899
61
SUZ12-20075857
68
EGR1-20690147
83
TCF3-18347094
47
WT1-20215353
39
FOX2A-19822575
51
MYC-19915707
49
NANOG-18692474
49
SMAD2-18955504
38
SMAD3-18955504
38
SOX2-18692474
51
SUZ12-18692474
37
PRDM14-21183938
37
POU5F1-18692474
58
EP300-20729851
38
NANOG-18347094
36
CLOCK-20551151
17
TAL1-20566737
35
KLF4-18358816
32
NACC1-18358816
21
GATA1-19941827
33
ZFP281-18757296
34
POU5F1-18347094
35
YAP1-20516196
37
TP53-20018659
24
NR0B1-18358816
30
SALL4-18804426_ESC
23
STAT4-19710469
32
EOMES-20176728
30
ESR1-21235772
11
NR1I2-20693526
21
STAT3-19079543
21
AR-19668381
45
TCF3-18692474
25
WT1-19549856
10
GATA2-19941826
35
SETDB1-19884255
31
SOX2-21211035
43
Targets/Database
2564
6083
2667
3565
4356
6207
2221
1663
2968
2979
3052
1936
1936
3319
1909
1944
4233
2093
1908
407
1875
1700
769
1834
2004
2109
2329
1123
1691
1065
1939
1744
228
939
948
3519
1351
199
2410
2020
3420
p-Value
8.10E-20
2.65E-19
1.13E-17
3.35E-15
4.23E-15
6.34E-15
6.66E-15
9.06E-14
1.05E-12
1.53E-11
3.56E-11
3.59E-11
3.59E-11
6.03E-11
9.64E-11
1.59E-10
1.71E-10
3.21E-10
3.69E-10
4.34E-10
8.87E-10
4.26E-09
6.01E-09
6.96E-09
1.66E-08
1.70E-08
1.90E-08
4.60E-08
4.99E-08
7.46E-08
8.65E-08
9.65E-08
1.44E-07
1.63E-07
1.90E-07
2.45E-07
3.41E-07
3.75E-07
4.08E-07
6.62E-07
7.61E-07