a
signal transduction
G-protein coupled receptor signaling pathway
transcription, DNA-dependent
small GTPase mediated signal transduction
protein phosphorylation
positive regulation of transcription, DNA-dependent
positive regulation of transcription from RNA polymerase II promoter
modulation by virus of host morphology or physiology
innate immune response
GTP catabolic process
0
1
2
3
4
# of DMRs
b
protein binding
DNA binding
ATP binding
protein dimerization activity
transferase activity, transfer phosphorus-containing grps
protein tyrosine kinase activity
protein kinase activity
0
2
4
6
8
10
12
14
7
8
9
# of DMRs
c
integral component of membrane
plasma membrane
nucleus
membrane
cytoplasm
mitochondrion
transcription factor complex
intracellular
perinuclear region of cytoplasm
cytosol
endoplasmic reticulum
0
1
2
3
4
5
6
# of DMRs
Fig. S1. Common gene ontology terms for the 26 annotated resident vs. migrant DMRs. (a)
Biological processes shared between two or more genes, (b) Molecular functions shared between
three or more genes, (c) Cellular components shared between two or more genes. Refer to Table
S3 for full list of all gene ontology terms identified for these genes.
a
b
Fig. S2. Gene networks identified using Ingenuity Pathway Analysis. Genes color indicates
methylation level for resident compared to migrant phenotype (blue = decreased, green =
increased). (a) Network 1 contains 15 of the annotated DMR genes and is involved in cellular
assembly and organization, cellular compromise, nervous system development and function. (b)
Network 2 contains 11 of the annotated DMR genes and is involved in nervous system
development and function, organ morphology, organismal development.
Table S1. Read counts and alignments to French and U.S. rainbow trout genomes for resident and smolt individuals
Uniquely
Mapped
ID #
Sample Name
Phenotype Sex
Unfiltered
Filtered
(French)
Sample 1
Resident_Female_2C11
Resident
Female
18,867,351
16,686,974
5,670,400
Sample 2
Resident_Female_0D10
Resident
Female
36,498,415
32,271,338
10,607,708
Sample 3
Resident_Male_237F
Resident
Male
32,286,475
28,177,042
9,502,951
Sample 4
Resident_Female_354C
Resident
Female
57,137,794
49,097,501
16,783,402
Sample 5
Resident_Male_3F40
Resident
Male
14,493,262
12,624,913
4,202,494
Sample 6
Resident_Female_1B1D
Resident
Female
23,434,854
18,131,957
5,868,018
Sample 7
Resident_Male_0931
Resident
Male
23,249,419
19,505,607
6,547,100
Sample 8
Resident_Male_7443
Resident
Male
32,911,920
25,890,555
8,584,749
Sample 9
Resident_Male_264D
Resident
Male
56,913,401
45,251,857
14,664,596
Sample 10
Resident_Female_3F1D
Smolt
Female
86,013,558
71,046,131
24,032,778
Sample 11
Smolt_Male_3944
Smolt
Male
22,280,323
19,781,458
6,617,372
Sample 12
Smolt_Female_2615
Smolt
Female
16,187,577
14,407,737
4,801,539
Sample 13
Smolt_Female_0307
Smolt
Female
19,471,076
17,127,341
4,969,150
Sample 14
Smolt_Male_3B14
Smolt
Male
15,673,647
13,615,959
4,565,537
Sample 15
Smolt_Female_1478
Smolt
Female
13,560,140
11,848,326
3,994,992
Sample 16
Smolt_Female_17D52
Smolt
Female
55,188,890
42,236,943
13,782,385
Sample 17
Smolt_Female_3C59
Smolt
Female
28,454,190
23,443,419
7,839,277
Sample 18
Smolt_Male_1110
Smolt
Male
22,176,655
18,843,847
6,369,487
Sample 19
Smolt_Male_703A
Smolt
Male
4,871,811
4,326,909
1,497,464
Sample 20
Smolt_Male_6867
Smolt
Male
5,989,529
5,190,837
1,774,987
No
Alignments
(French)
5,557,121
10,501,193
9,715,102
16,271,796
4,341,122
8,831,983
9,201,364
12,297,102
21,238,060
33,019,374
6,495,418
4,917,828
5,791,804
4,601,578
4,012,600
20,502,613
11,114,423
8,802,748
1,416,945
1,727,239
Uniquely
Mapped
(U.S.)
4,048,241
7,723,728
6,960,642
12,253,998
3,084,436
4,318,413
4,818,466
6,333,517
10,746,986
17,609,970
4,940,367
3,524,056
3,973,436
3,346,697
2,949,388
10,046,720
5,745,762
4,620,518
1,097,560
1,330,270
No
Alignments
(U.S.)
5,252,784
9,383,775
9,460,362
15,214,137
4,135,391
8,853,159
9,180,180
12,367,287
21,151,397
32,819,185
6,097,482
4,639,955
5,494,795
4,380,791
3,821,725
20,463,569
11,159,454
8,720,543
1,331,074
1,620,752
Table S2. Detailed information for differentially methylated regions (DMRs) when comparing juvenile resident and migratory O. mykiss phenotypes. DMRs with two rows of data represent hits to both French and Miller rainbow trout genomes.
CpG island
Start
Meth diff 1 # of CpGs # of DMCs
p-value q-value Contig_scaffold
position
Symbol
Entrez gene name
Functional genomic distribution Chromosome context
AATK
apoptosis-associated tyrosine kinase
<5kb upstream of TSS
Unknown
open%sea
-20.7
3
2
1.1E-21 1.4E-21 FR907459_3187
6454
ADHFE1
Alcohol Dehydrogenase, Iron Containing, 1
<5kb upstream of TSS
Omy19
open%sea
-38.2
3
2
6.2E-29 9.9E-29 MMSRT025C_2075_1
43636
ADORA3
adenosine A3 receptor
Gene body
Omy7
open%sea
-23.5
7
4
5.4E-45 2.4E-44 FR904328_63
1466297
(23.6
7
4
3.7E(46
1.4E(45 MMSRT001B_scaff_1733_1
22090
AHR2A
aryl hydrocarbon receptor 2 alpha
5-10kb upstream of TSS
Unknown
shore
31.9
4
3
1.1E-43 3.6E-43 MMSRT073E_1706_1
3003
CCDC93
coiled-coil domain containing 93
Gene body
Omy3
shore
20.7
3
1
6.8E-18 8.6E-18 FR905754_1482
115054
CD247
CD247 molecule
<5kb upstream of TSS
Unknown
open%sea
22.8
5
2
3.2E-34 6.3E-34 FR906353_2081
23649
CLDN10
claudin 10
Gene body
Omy3
open%sea
29.5
3
3
3.0E-36 6.8E-36 MMSRT042G_1581_2
35928
CRYBB3
crystallin, beta B3
Gene body
Omy7
island
21.3
4
1
1.0E-35 2.1E-35 FR904434_167
1335767
21.1
4
1
4.6E(38
1.2E(37 MMSRT117A_scaff_1889_1
19751
DDX10
DEAD (Asp-Glu-Ala-Asp) box polypeptide 10
<1.5kb downstream of stop codon Omy10
open%sea
29.5
4
3
1.2E-31 2.2E-31 FR904727_455
284644
GEMIN2
gem (nuclear organelle) associated protein 2
Gene body
Omy19
open%sea
-34.1
3
2
2.5E-30 4.1E-30 FR904474_207
438741
(34.2
3
2
1.6E(30
2.6E(30 MMSRT071A_scaff_3011_1
47548
GRM1
glutamate receptor, metabotropic 1
Gene body
Omy19
shore
-31.3
7
5
1.2E-53 1.0E-52 FR904329_64
922718
(28.4
8
5
7.6E(48
4.1E(47 MMSRT062C_scaff_2450_1
26458
HES6
hes family bHLH transcription factor 6
<5kb upstream of TSS
Unknown
shore
-20.7
3
1
2.2E-14 2.6E-14 FR905566_1294
184909
KIAA1467
KIAA1467
<5kb upstream of TSS
Omy4
shore
23.2
4
1
1.8E-17 2.2E-17 FR905145_873
106914
23.1
4
1
1.2E(17
1.5E(17 MMSRT069B_scaff_1646_1
26732
MYOM3
myomesin 3
<5kb upstream of TSS
Omy3
island
-21.7
3
1
7.9E-10 8.0E-10 FR904357_92
399171
(21.7
3
1
9.0E(10
9.0E(10 MMSRT026G_scaff_1716_2
87415
NEUROD4
neurogenic differentiation 4
<1.5kb downstream of stop codon Unknown
shore
-31.4
3
2
8.3E-36 1.8E-35 FR906233_1961
31266
(31.7
3
2
4.3E(36
8.2E(36 MMSRT142F_scaff_3021_1
14688
NHLH2
nescient helix loop helix 2
Gene body
Omy3
shore
38.0
14
12
3.2E-76 1.4E-74 FR907983_3711
31771
PALLD
palladin, cytoskeletal associated protein
Gene body
Omy22
island
24.4
8
2
7.2E-62 7.9E-61 FR904673_401
443036
PCDHGC5
protocadherin gamma subfamily C, 5
Gene body
Omy10
shore
48.8
5
5
3.1E-49 1.7E-48 FR905400_1128
190015
RASD1
RAS, dexamethasone-induced 1
5-10kb upstream of TSS
Omy20
open%sea
21.5
3
1
1.8E-16 2.2E-16 FR905370_1098
150900
RGL2
ral guanine nucleotide dissociation stimulator-like 2 5-10kb upstream of TSS
Unknown
shore
21.2
3
1
1.2E-15 1.3E-15 MMSRT050A_1640_1
26199
RSAD2
radical S-adenosyl methionine domain containing 2 <1.5kb downstream of stop codon Unknown
open%sea
-61.8
10
10
2.7E-69 5.9E-68 FR908501_4229
32535
SBK1
serine/threonine-protein kinase SBK1-like
Gene body
Omy12
island
-28.6
21
10
7.0E-86 1.9E-84 MMSRT118F_1666_1
68899
SETD3
SET domain containing 3
Gene body
Omy19
open%sea
42.5
6
6
5.4E-53 4.0E-52 FR904415_148
55876
41.9
6
6
2.5E(53
2.2E(52 MMSRT017H_scaff_1643_3
51803
STYK1
serine/threonine/tyrosine kinase 1
<1.5kb downstream of stop codon Unknown
open%sea
28.3
4
3
3.5E-40 1.3E-39 FR904869_597
536451
TMEM150A
transmembrane protein 150A
Gene body
Omy16
open%sea
-23.6
3
1
6.4E-24 8.7E-24 MMSRT054E_1746_6
43876
TUBA1A
tubulin, alpha 1a
Gene body
Unknown
shelf
-26.9
3
3
9.1E-34 1.7E-33 FR906595_2323
32581
Uncharacterized protein
Gene body
Omy10
open%sea
42.0
3
2
1.2E-30 2.1E-30 FR904314_49
1898070
Uncharacterized protein
Gene body
Omy10
open%sea
-21.1
3
1
1.3E-10 1.3E-10 FR905562_1290
143025
Uncharacterized protein
5-10kb upstream of TSS
Unknown
shore
-21.7
3
1
2.7E-11
3.0E-11 FR905963_1691
136118
Uncharacterized protein
<5kb upstream of TSS
Unknown
open%sea
-31.7
3
3
8.3E-36 1.8E-35 FR907215_2943
53300
Uncharacterized protein
<5kb upstream of TSS
Unknown
shore
-32.3
3
2
1.4E-22 1.7E-22 MMSRT031A_2343_2
1255
Unknown
Intergenic
Omy16
shelf
-21.0
4
1
7.9E-29 1.2E-28 MMSRT032D_1742_1
27068
Unknown
Intergenic
Omy23
island
-33.8
4
3
1.2E-43 3.6E-43 MMSRT040D_1677_1
1103
Unknown
Intergenic
Omy10
shelf
20.6
3
1
1.1E-09 1.1E-09 FR904314_49
242508
Unknown
Intergenic
Omy20
shelf
23.7
3
1
2.0E-28 3.2E-28 FR904322_57
1755512
Unknown
Intergenic
Omy19
open%sea
26.2
5
4
2.1E-38 7.1E-38 FR904329_64
1826731
Unknown
Intergenic
Omy19
island
-30.0
4
4
2.2E-42 8.9E-42 FR904351_86
1584879
Unknown
Intergenic
Omy19
open%sea
31.9
3
3
8.3E-36 1.8E-35 FR904415_148
592107
31.8
3
3
4.3E(36
8.2E(36 MMSRT060F_scaff_1688_1
62484
Unknown
Intergenic
Omy19
open%sea
29.1
5
4
5.3E-46 2.6E-45 FR904429_162
575928
29.0
5
4
1.7E(46
7.7E(46 MMSRT063E_scaff_1784_1
8960
Unknown
Intergenic
Omy16
shelf
21.3
3
1
3.9E-23 5.5E-23 FR904526_258
841950
Unknown
Intergenic
Omy29
open%sea
-20.2
5
1
1.4E-31 2.4E-31 FR904607_337
911205
Unknown
Intergenic
Omy10
open%sea
-22.3
5
1
6.7E-37 2.0E-36 FR904613_343
800481
End
position
6492
43686
1466486
22279
3134
115078
23792
36051
1335800
19784
284771
438786
47593
922934
26854
184937
106945
26763
399220
87464
31311
14733
32052
443147
190108
151030
26248
32903
69369
55921
51848
536500
43999
32732
1898089
143149
136449
53349
1415
27409
1149
242747
1755633
1826844
1584920
592154
62531
576081
9113
842094
911311
800527
Table S2 Cont.
-
Unknown
Intergenic
Unknown
island
-23.7
(27.2
Unknown
Intergenic
Omy16
shelf
-24.0
Unknown
Intergenic
Omy10
island
-20.5
(20.5
Unknown
Intergenic
Unknown
open%sea
30.5
Unknown
Intergenic
Unknown
open%sea
20.6
20.2
Unknown
Intergenic
Unknown
island
-21.6
Unknown
Intergenic
Omy3
open%sea
24.4
Unknown
Intergenic
Unknown
open%sea
26.6
Unknown
Intergenic
Unknown
shore
-31.3
Unknown
Intergenic
Unknown
open%sea
-31.0
Unknown
Intergenic
Omy20
open%sea
20.1
Unknown
Intergenic
Unknown
shelf
-23.1
Unknown
Intergenic
Omy4
island
35.4
Unknown
Intergenic
Omy15
open%sea
22.0
Unknown
Intergenic
Omy19
open%sea
-26.3
1
Percent methylation differences averaged from all CpG sites within the defined region. The comparison is residents compared to migrants (i.e., smolts).
5
5
4
3
3
3
3
3
3
3
3
9
3
8
4
7
3
4
2
5
2
1
1
1
1
1
2
2
1
5
3
3
3
5
2
1
2.8E-49
3.7E(50
6.8E-38
1.9E-11
4.2E(11
5.3E-23
4.6E-11
6.8E(11
2.1E-23
8.3E-36
6.1E-28
1.5E-65
8.3E-36
6.9E-37
6.1E-33
8.7E-60
8.7E-27
7.5E-22
1.7E-48
2.5E(49
2.1E-37
2.1E-11
4.6E(11
7.3E-23
4.9E-11
7.1E(11
3.0E-23
1.8E-35
9.3E-28
2.2E-64
1.8E-35
1.7E-36
1.1E-32
1.2E-58
1.2E-26
1.0E-21
FR904682_410
MMSRT007A_scaff_1463_1
FR904705_433
FR904748_476
MMSRT057A_scaff_1596_2
FR904859_587
FR905135_863
MMSRT023H_scaff_1491_1
FR905506_1234
FR905521_1249
FR905721_1449
FR906155_1883
FR906735_2463
MMSRT010E_1934_5
MMSRT027B_2013_1
MMSRT094H_2242_1
MMSRT108D_1238_1
FR904635
680456
76264
776886
605820
35196
347754
384237
88585
241073
262928
216024
22526
26692
90125
12107
35302
74665
340968
680564
76412
776928
605846
35222
347772
384277
88625
241089
262969
216071
22653
26738
90269
12259
35391
74674
341014
Table S3. Gene ontology full details for each DMR annotated gene when comparing resident and
migrant O. mykiss juvenile phenotypes
Biological Process
Evidence1
PubMed
Reference
protein serine/threonine kinase activity
IEA
--
GO:0005524
ATP binding
IEA
--
AATK
GO:0004672
protein kinase activity
--
--
AATK
GO:0004713
protein tyrosine kinase activity
AATK
GO:0005515
AATK
GO:0016772
protein binding
transferase activity, transferring phosphoruscontaining groups
ADHFE1
GO:0006103
2-oxoglutarate metabolic process
ADHFE1
GO:0015993
ADHFE1
GO:0044237
ADHFE1
GO:0055114
oxidation-reduction process
ADHFE1
GO:0044281
small molecule metabolic process
ADORA3
GO:0001973
adenosine receptor signaling pathway
ADORA3
GO:0002553
histamine secretion by mast cell
ADORA3
GO:0002687
positive regulation of leukocyte migration
IEA
--
ADORA3
GO:0006954
inflammatory response
TAS
9164961
ADORA3
GO:0007190
activation of adenylate cyclase activity
TAS
9380026
ADORA3
GO:0007186
--
--
ADORA3
GO:0050850
G-protein coupled receptor signaling pathway
positive regulation of calcium-mediated
signaling
IEA
--
ADORA3
GO:0050729
positive regulation of inflammatory response
IEA
--
ADORA3
GO:0043306
positive regulation of mast cell degranulation
IEA
--
ADORA3
GO:0070257
IEA
--
ADORA3
GO:0014068
positive regulation of mucus secretion
positive regulation of phosphatidylinositol 3kinase signaling
IEA
--
ADORA3
GO:0008016
regulation of heart contraction
TAS
9837869
ADORA3
GO:0009611
response to wounding
TAS
9837869
ADORA3
GO:0007165
signal transduction
TAS
8399349
AHR
GO:0001568
NAS
19538249
AHR
GO:0000122
blood vessel development
negative regulation of transcription from RNA
polymerase II promoter
IEA
--
AHR
GO:0006355
IDA
10395741
AHR
GO:0006357
regulation of transcription, DNA-dependent
regulation of transcription from RNA
polymerase II promoter
IDA
15681594
AHR
GO:0006366
transcription from RNA polymerase II promoter
IDA
10395741
AHR
GO:0006915
TAS
12213388
AHR
GO:0045893
apoptotic process
positive regulation of transcription, DNAdependent
--
--
AHR
GO:0007049
cell cycle
TAS
12213388
AHR
GO:0048732
gland development
--
--
Gene Symbol
ID
GO term
AATK
GO:0004674
AATK
IEA
--
IPI
14521924
--
--
TAS
--
molecular hydrogen transport
IDA
16435184
cellular metabolic process
TAS
--
--
--
TAS
--
--
--
IEA
--
Table S3 Cont.
AHR
GO:0030522
intracellular receptor signaling pathway
IDA
10395741
AHR
GO:0045899
positive regulation of RNA polymerase II
transcriptional preinitiation complex assembly
IEA
--
AHR
GO:0030850
prostate gland development
IEA
--
AHR
GO:0030888
regulation of B cell proliferation
IDA
15681594
AHR
GO:0010468
regulation of gene expression
IDA
15681594
AHR
GO:0048608
reproductive structure development
--
--
AHR
GO:0006950
response to stress
IDA
7961644
AHR
GO:0009410
response to xenobiotic stimulus
IDA
7961644
AHR
GO:0007165
signal transduction
--
--
AHR
GO:0006805
xenobiotic metabolic process
TAS
19538249
CD247
GO:0007166
cell surface receptor signaling pathway
--
--
CD247
GO:0016032
TAS
--
CD247
GO:0019048
viral process
modulation by virus of host morphology or
physiology
IEA
--
CD247
GO:0031295
TAS
--
CD247
GO:0038096
T cell costimulation
Fc-gamma receptor signaling pathway involved
in phagocytosis
TAS
--
CD247
GO:0045087
innate immune response
TAS
--
CD247
GO:0050690
regulation of defense response to virus by virus
TAS
--
CD247
GO:0050776
regulation of immune response
TAS
--
CD247
GO:0050852
T cell receptor signaling pathway
TAS
--
CLDN10
GO:0007155
cell adhesion
TAS
10508613
CLDN10
GO:0016338
calcium-independent cell-cell adhesion
ISS
--
CRYBB3
GO:0007601
visual perception
TAS
8999933
GEMIN2
GO:0000245
spliceosomal complex assembly
IEA
--
GEMIN2
GO:0000375
RNA splicing, via transesterification reactions
TAS
9323129
GEMIN2
GO:0000387
spliceosomal snRNP assembly
TAS
--
GEMIN2
GO:0006397
mRNA processing
TAS
9323130
GEMIN2
GO:0008380
RNA splicing
TAS
9323129
GEMIN2
GO:0010467
gene expression
TAS
--
GEMIN2
GO:0016070
RNA metabolic process
TAS
--
GEMIN2
GO:0034660
ncRNA metabolic process
TAS
--
GRM1
GO:0000186
activation of MAPKK activity
IEA
--
GRM1
GO:0000187
activation of MAPK activity
IEA
--
GRM1
GO:0007186
G-protein coupled receptor signaling pathway
TAS
7476890
GRM1
GO:0007268
synaptic transmission
TAS
9076744
GRM1
GO:0007626
locomotory behavior
IEA
--
GRM1
GO:0008219
cell death
IEA
--
GRM1
GO:0019233
sensory perception of pain
IEA
--
GRM1
GO:0043408
regulation of MAPK cascade
--
--
GRM1
GO:0071257
cellular response to electrical stimulus
IEA
--
Table S3 Cont.
GRM1
GO:0051930
regulation of sensory perception of pain
IEA
--
NHLH2
GO:0006351
transcription, DNA-dependent
IEA
--
NHLH2
GO:0007417
central nervous system development
TAS
1328219
NHLH2
GO:0030154
IEA
--
NHLH2
GO:0045944
cell differentiation
positive regulation of transcription from RNA
polymerase II promoter
TAS
16314316
NHLH2
GO:0007617
mating behavior
IEA
--
NHLH2
GO:0042698
ovulation cycle
IEA
--
NHLH2
GO:0051091
positive regulation of sequence-specific DNA
binding transcription factor activity
TAS
16314316
PALLD
GO:0007010
cytoskeleton organization
NAS
11598191
PCDHGC5
GO:0007156
homophilic cell adhesion
IEA
--
RASD1
GO:0007165
signal transduction
TAS
10471929
RASD1
GO:0006913
nucleocytoplasmic transport
--
--
RASD1
GO:0006184
GTP catabolic process
--
--
RASD1
GO:0006886
intracellular protein transport
--
--
RASD1
GO:0007186
TAS
10840027
RASD1
GO:0045892
G-protein coupled receptor signaling pathway
negative regulation of transcription, DNAdependent
IEA
--
RASD1
GO:0007263
nitric oxide mediated signal transduction
IEA
--
RASD1
GO:0015031
protein transport
--
--
RASD1
GO:0007264
small GTPase mediated signal transduction
IEA
--
RGL2
GO:0007264
small GTPase mediated signal transduction
--
--
RGL2
GO:0007165
signal transduction
--
--
RGL2
GO:0007265
Ras protein signal transduction
NAS
8976381
RGL2
GO:0032318
NAS
8976381
RGL2
GO:0051056
regulation of Ras GTPase activity
regulation of small GTPase mediated signal
transduction
--
--
RSAD2
GO:0001503
ossification
IEA
--
RSAD2
GO:0009615
IDA
--
RSAD2
GO:0019048
response to virus
modulation by virus of host morphology or
physiology
IEA
--
RSAD2
GO:0030278
IEA
--
RSAD2
GO:0034157
ISS
--
RSAD2
GO:0034165
regulation of ossification
positive regulation of toll-like receptor 7
signaling pathway
positive regulation of toll-like receptor 9
signaling pathway
ISS
--
RSAD2
GO:0035710
CD4-positive, alpha-beta T cell activation
ISS
--
RSAD2
GO:0043367
CD4-positive, alpha-beta T cell differentiation
ISS
--
RSAD2
GO:0051607
defense response to virus
IDA
16108059
RSAD2
GO:0045087
innate immune response
IEA
--
RSAD2
GO:0050709
negative regulation of protein secretion
IDA
19074433
RSAD2
GO:0045071
IDA
--
RSAD2
GO:2000553
negative regulation of viral genome replication
positive regulation of T-helper 2 cell cytokine
production
ISS
--
Table S3 Cont.
SBK1
GO:0006468
protein phosphorylation
--
--
SETD3
GO:0006351
transcription, DNA-dependent
IEA
--
SETD3
GO:0010452
histone H3-K36 methylation
ISS
--
SETD3
GO:0051568
histone H3-K4 methylation
--
--
SETD3
GO:0018027
peptidyl-lysine dimethylation
ISS
--
SETD3
GO:0018026
peptidyl-lysine monomethylation
ISS
--
SETD3
GO:0018023
peptidyl-lysine trimethylation
ISS
--
SETD3
GO:0051149
IEA
--
SETD3
GO:0045944
IEA
--
SETD3
GO:0045893
positive regulation of muscle cell differentiation
positive regulation of transcription from RNA
polymerase II promoter
positive regulation of transcription, DNAdependent
ISS
--
STYK1
GO:0006468
protein phosphorylation
--
--
TMEM150A
GO:0009056
catabolic process
IEA
--
TUBA1A
GO:0051084
'de novo' posttranslational protein folding
TAS
--
TUBA1A
GO:0000086
G2/M transition of mitotic cell cycle
TAS
--
TUBA1A
GO:0000226
microtubule cytoskeleton organization
--
--
TUBA1A
GO:0000278
mitotic cell cycle
TAS
--
TUBA1A
GO:0006184
GTP catabolic process
--
--
TUBA1A
GO:0006457
protein folding
TAS
--
TUBA1A
GO:0051301
cell division
TAS
12090300
TUBA1A
GO:0044267
cellular protein metabolic process
TAS
--
TUBA1A
GO:0030705
cytoskeleton-dependent intracellular transport
TAS
12090300
TUBA1A
GO:0007017
microtubule-based process
TAS
12090300
TUBA1A
GO:0051258
protein polymerization
IEA
--
Evidence1
PubMed
Reference
Molecular Function
Gene Symbol
ID
GO term
AATK
GO:0004674
protein serine/threonine kinase activity
IEA
--
AATK
GO:0005524
ATP binding
IEA
--
AATK
GO:0004672
protein kinase activity
--
--
AATK
GO:0004713
protein tyrosine kinase activity
AATK
GO:0005515
AATK
GO:0016772
protein binding
transferase activity, transferring phosphoruscontaining groups
ADHFE1
GO:0016491
oxidoreductase activity
ADHFE1
GO:0046872
metal ion binding
IEA
--
ADHFE1
GO:0047988
hydroxyacid-oxoacid transhydrogenase activity
IDA
16435184
ADORA3
GO:0001609
G-protein coupled adenosine receptor activity
IEA
--
ADORA3
GO:0004930
--
--
AHR
GO:0003700
G-protein coupled receptor activity
sequence-specific DNA binding transcription
factor activity
IDA
11782478
IEA
--
IPI
14521924
--
--
--
--
Table S3 Cont.
AHR
GO:0003677
DNA binding
RNA polymerase II distal enhancer sequencespecific DNA binding transcription factor
activity
TAS
19538249
AHR
GO:0003705
IEA
--
AHR
GO:0004871
AHR
GO:0004879
signal transducer activity
ligand-activated sequence-specific DNA
binding RNA polymerase II transcription factor
activity
--
--
AHR
GO:0008134
transcription factor binding
IDA
10395741
IPI
9079689
AHR
GO:0044212
transcription regulatory region DNA binding
IDA
15681594
AHR
GO:0051879
Hsp90 protein binding
IDA
9079689
AHR
GO:0043565
sequence-specific DNA binding
IEA
--
AHR
GO:0046983
protein dimerization activity
TAS
19538249
AHR
GO:0046982
protein heterodimerization activity
TAS
19538249
AHR
GO:0005515
protein binding
IPI
10395741
CD247
GO:0004888
transmembrane signaling receptor activity
IEA
--
CD247
GO:0005515
protein binding
IPI
10704231
CD247
GO:0042802
identical protein binding
IPI
17055436
CD247
GO:0042803
protein homodimerization activity
NAS
12110186
CLDN10
GO:0005198
structural molecule activity
IEA
--
CLDN10
GO:0042802
identical protein binding
ISS
--
CRYBB3
GO:0005212
structural constituent of eye lens
IEA
--
DDX10
GO:0005524
ATP binding
IEA
--
DDX10
GO:0008026
ATP-dependent helicase activity
IEA
--
DDX10
GO:0004386
helicase activity
--
--
DDX10
GO:0003676
nucleic acid binding
--
--
DDX10
GO:0003723
RNA binding
IEA
--
DDX10
GO:0003724
RNA helicase activity
TAS
8660968
GEMIN2
GO:0005515
protein binding
IPI
11714716
GRM1
GO:0004930
G-protein coupled receptor activity
TAS
7476890
GRM1
GO:0005515
protein binding
IPI
19084525
GRM1
GO:0008066
glutamate receptor activity
TAS
7476890
HES6
GO:0003677
IEA
--
HES6
GO:0003700
DNA binding
sequence-specific DNA binding transcription
factor activity
IEA
--
HES6
GO:0046983
protein dimerization activity
IEA
--
HES6
GO:0003712
transcription cofactor activity
ISS
10851137
HES6
GO:0008134
transcription factor binding
NAS
17611704
MYOM3
GO:0005515
protein binding
--
--
MYOM3
GO:0042803
protein homodimerization activity
ISS
--
NEUROD4
GO:0003677
DNA binding
IEA
--
NEUROD4
GO:0046983
protein dimerization activity
IEA
--
Table S3 Cont.
NHLH2
GO:0001102
RNA polymerase II activating transcription
factor binding
NHLH2
GO:0003677
NHLH2
IPI
16314316
DNA binding
IEA
--
GO:0046983
protein dimerization activity
IEA
--
NHLH2
GO:0005515
protein binding
IPI
--
PALLD
GO:0003779
actin binding
IEA
--
PALLD
GO:0005515
protein binding
IPI
11598191
PALLD
GO:0051371
muscle alpha-actinin binding
TAS
16125169
PCDHGC5
GO:0005509
calcium ion binding
IEA
--
RASD1
GO:0005525
GTP binding
IEA
--
RASD1
GO:0003924
GTPase activity
IEA
--
RASD1
GO:0005515
protein binding
--
--
RGL2
GO:0005088
Ras guanyl-nucleotide exchange factor activity
NAS
8976381
RGL2
GO:0005085
guanyl-nucleotide exchange factor activity
--
--
RSAD2
GO:0003674
molecular_function
ND
--
RSAD2
GO:0003824
catalytic activity
IEA
--
RSAD2
GO:0005515
protein binding
IPI
--
RSAD2
GO:0043621
protein self-association
IDA
19074433
RSAD2
GO:0046872
metal ion binding
IEA
--
RSAD2
GO:0051536
iron-sulfur cluster binding
--
--
RSAD2
GO:0051539
4 iron, 4 sulfur cluster binding
IDA
--
SBK1
GO:0004672
protein kinase activity
--
--
SBK1
GO:0005524
ATP binding
IEA
--
SBK1
GO:0004674
protein serine/threonine kinase activity
IEA
--
SBK1
GO:0004713
--
--
SBK1
GO:0016772
--
--
SETD3
GO:0001102
protein tyrosine kinase activity
transferase activity, transferring phosphoruscontaining groups
RNA polymerase II activating transcription
factor binding
IEA
--
SETD3
GO:0003713
ISS
--
SETD3
GO:0046975
ISS
--
SETD3
GO:0042800
transcription coactivator activity
histone methyltransferase activity (H3-K36
specific)
histone methyltransferase activity (H3-K4
specific)
IEA
--
SETD3
GO:0005515
protein binding
--
--
STYK1
GO:0004672
protein kinase activity
--
--
STYK1
GO:0004713
protein tyrosine kinase activity
--
--
STYK1
GO:0005524
IEA
--
STYK1
GO:0004715
ATP binding
non-membrane spanning protein tyrosine kinase
activity
IEA
--
STYK1
GO:0005515
IPI
--
STYK1
GO:0016772
--
--
protein binding
transferase activity, transferring phosphoruscontaining groups
Table S3 Cont.
TUBA1A
GO:0003924
GTPase activity
IEA
--
TUBA1A
GO:0005198
structural molecule activity
TAS
12090300
TUBA1A
GO:0005200
structural constituent of cytoskeleton
IEA
--
TUBA1A
GO:0005515
protein binding
IPI
19893491
TUBA1A
GO:0005525
GTP binding
IEA
--
TUBA1A
GO:0019904
protein domain specific binding
IEA
--
Evidence1
PubMed
Reference
Cellular Component
Gene Symbol
ID
GO term
AATK
GO:0005783
endoplasmic reticulum
IEA
--
AATK
GO:0048471
perinuclear region of cytoplasm
IEA
--
AATK
GO:0005739
mitochondrion
--
--
AATK
GO:0016021
integral component of membrane
IEA
--
AATK
GO:0044295
axonal growth cone
IEA
--
AATK
GO:0055037
recycling endosome
IEA
--
ADHFE1
GO:0005739
mitochondrion
ISS
--
ADHFE1
GO:0005759
mitochondrial matrix
TAS
--
ADORA3
GO:0005886
plasma membrane
TAS
--
ADORA3
GO:0005887
integral component of plasma membrane
IEA
--
ADORA3
GO:0016021
integral component of membrane
IEA
--
ADORA3
GO:0042629
mast cell granule
IEA
--
AHR
GO:0005667
transcription factor complex
TAS
19538249
AHR
GO:0005634
nucleus
IDA
--
AHR
GO:0005730
NOT nucleolus
IDA
--
AHR
GO:0005737
cytoplasm
IDA
--
AHR
GO:0034752
cytosolic aryl hydrocarbon receptor complex
TAS
19538249
CD247
GO:0005737
cytoplasm
IDA
11390434
CD247
GO:0005886
plasma membrane
TAS
--
CD247
GO:0016020
membrane
--
--
CD247
GO:0016021
integral to membrane
IEA
--
CD247
GO:0042101
T cell receptor complex
IDA
8176201
CD247
GO:0042105
alpha-beta T cell receptor complex
IEA
--
CLDN10
GO:0005886
plasma membrane
IEA
--
CLDN10
GO:0005923
tight junction
ISS
--
CLDN10
GO:0016020
membrane
--
--
CLDN10
GO:0016021
integral to membrane
IEA
--
GEMIN2
GO:0005622
intracellular
--
--
GEMIN2
GO:0005634
nucleus
TAS
9323130
Table S3 Cont.
GEMIN2
GO:0005654
nucleoplasm
TAS
--
GEMIN2
GO:0005681
spliceosomal complex
IEA
--
GEMIN2
GO:0005737
cytoplasm
TAS
9323130
GEMIN2
GO:0005829
cytosol
TAS
--
GEMIN2
GO:0015030
Cajal body
--
--
GEMIN2
GO:0097504
Gemini of coiled bodies
IEA
--
GRM1
GO:0005634
nucleus
IEA
--
GRM1
GO:0005886
plasma membrane
TAS
--
GRM1
GO:0005887
integral to plasma membrane
TAS
7476890
GRM1
GO:0014069
postsynaptic density
IEA
--
GRM1
GO:0016021
integral to membrane
--
--
GRM1
GO:0030425
IEA
--
GRM1
GO:0038038
dendrite
G-protein coupled receptor homodimeric
complex
IPI
10945991
GRM1
GO:0043005
neuron projection
--
--
HES6
GO:0005634
nucleus
IEA
--
HES6
GO:0005667
transcription factor complex
ISS
10851137
MYOM3
GO:0031430
M band
ISS
--
NEUROD4
GO:0005634
nucleus
IEA
--
NHLH2
GO:0005634
nucleus
IEA
--
NHLH2
GO:0005667
transcription factor complex
TAS
16314316
PALLD
GO:0001726
ruffle
IEA
--
PALLD
GO:0005634
nucleus
IDA
11598191
PALLD
GO:0005884
actin filament
IDA
11598191
PALLD
GO:0005925
focal adhesion
IEA
--
PALLD
GO:0030018
Z disc
IEA
--
PCDHGC5
GO:0005886
plasma membrane
IEA
--
PCDHGC5
GO:0016020
membrane
--
--
PCDHGC5
GO:0016021
integral to membrane
IEA
--
RASD1
GO:0016020
membrane
--
--
RASD1
GO:0005886
plasma membrane
IEA
--
RASD1
GO:0005622
intracellular
--
--
RASD1
GO:0005634
nucleus
IEA
--
RASD1
GO:0048471
perinuclear region of cytoplasm
IEA
--
RGL2
GO:0005622
intracellular
IEA
--
RGL2
GO:0005575
cellular_component
ND
--
RSAD2
GO:0005739
mitochondrion
IDA
--
RSAD2
GO:0005741
mitochondrial outer membrane
IDA
--
RSAD2
GO:0005743
mitochondrial inner membrane
IDA
--
Table S3 Cont.
RSAD2
GO:0005783
endoplasmic reticulum
IDA
11752458
RSAD2
GO:0005789
endoplasmic reticulum membrane
IDA
19074433
RSAD2
GO:0005794
Golgi apparatus
IEA
--
RSAD2
GO:0005811
lipid particle
ISS
--
SBK1
GO:0005737
cytoplasm
IEA
--
SETD3
GO:0000790
nuclear chromatin
IEA
--
STYK1
GO:0005886
plasma membrane
IDA
--
STYK1
GO:0016021
integral to membrane
IEA
--
TMEM150A
GO:0005886
plasma membrane
IEA
--
TMEM150A
GO:0016021
integral component of membrane
IEA
--
TUBA1A
GO:0005829
cytosol
TAS
--
TUBA1A
GO:0005874
microtubule
TAS
12090300
TUBA1A
GO:0005881
cytoplasmic microtubule
IEA
--
TUBA1A
GO:0015630
microtubule cytoskeleton
IDA
--
TUBA1A
GO:0043234
protein complex
--
--
1
Inference Codes: IDA = Direct Assay; IEA = Electronic Annotation; IPI = Physical Interaction; ISS = Sequence or
structural Similarity; NAS = Non-traceable Author Statement; ND = No biological Data available; TAS = Traceable
Author Statement
Table S4. Significant canonical pathways, functions, and top networks for the 26 annotated DMRs identified using Ingenuity Pathway Analysis.
Canonical Pathways
Name
Sertoli Cell-Sertoli Cell Junction Signaling
Role of Lipids/Lipid Rafts in the
Pathogenesis of Influenza
Cytotoxic T Lymphocyte-mediated
Apoptosis of Target Cells
Ethanol Degradation II
G-Protein Coupled Receptor Signaling
p-value
2.1E-02
3.1E-02
3.9E-02
4.1E-02
4.1E-02
Molecular and Cellular Functions
Name
Cellular Development
p-value
2.5E-04 - 4.4E-02
Cell Morphology
4.1E-04 - 4.1E-02
Cell-To-Cell Signaling and Interaction
Amino Acid Metabolism
Cell Cycle
9.3E-04 - 3.9E-02
1.3E-03 - 4.5E-02
1.3E-03 - 3.2E-02
# of
Genes Included DMR Genes
13 AATK, ADORA3, AHR, CD247, GEMIN2, HES6, NEUROD4,
PALLD, RASD1, RGL2, RSAD2, SETD3, TUBA1A
11 AATK, ADORA3, AHR, CD247, GRM1, KIAA1467,
NEUROD4, NHLH2, PALLD, PCDHGC5, TUBA1A
6 ADORA3, AHR, CD247, GRM1, PCDHGC5, PALLD
2 GRM1, SBK1
4 AHR, CD247, RGL2, TUBA1A
Physiological System Development and
Function
Name
Organ Morphology
Organismal Development
Reproductive System Development and
Function
Nervous System Development and Function
Auditory and Vestibular System
p-value
1.9E-04 - 4.3E-02
1.9E-04 - 4.7E-02
1.9E-04 - 4.2E-02
2.0E-04 - 4.5E-02
1.30E-03
# of
Genes Included DMR Genes
3 AHR, CD247, NHLH2,
2 ADORA3, NHLH2
4
AHR, CD247, GRM1, NHLH2
7 AATK, CD247, GRM1, NEUROD4, NHLH2, PALLD, TUBA1A
1 GRM1
Development and Function
Top Networks
Associated Network Functions
Cellular Assembly and Organization,
Cellular Compromise, Nervous System
Development and Function
Nervous System Development and
Function, Organ Morphology, Organismal
Development
ID_Score
1_38
2_26
# of
Genes Included DMR Genes
15 AATK, ADHFE1, CCDC93, CLDN10, CRYBB3, DDX10,
GEMIN2, HES6, KIAA1467, MYOM3, PALLD, PCDHGC5,
RGL2, SETD3, TMEM150A
11
ADORA3, AHR, CD247, GRM1, NEUROD4, NHLH2, RASD1,
RSAD2, SBK1, STYK1, TUBA1A