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Old Mapping New Mapping

Supplementary Material

Epigenetic histone modifications of human transposableelements: genome defense versus exaptationAhsan Huda, Leonardo Mariño-Ramírez and I. King Jordan

Supplementary Figure 1. Comparison of the original (old) mapping and new mapping procedures. (a) Number of tags of active histone tail modifications and (b) number of tags of repressive modifications mapped using the old and the new mapping techniques

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Supplementary Figure 2. Effect of individual histone modifications on CD4+ T cellgene expression levels. Histone tail modifications were determined to be present or absent in the promoter regions of human genes as described in the Methods section. For each modification, the log2 normalized ratio of the average expression level for genes present for the modification over the average expression level for genes where the modification is absent is shown. Active modifications (red) have positive ratios, andrepressive modifications (green) have negative ratios.

Supplementary Table 1. Statistics for histone modification enrichment or depletion in TEs and human gene expression. Significance was calculated using the G-test and the P-value was adjusted for multiple tests using the Bonferroni correction (refer to Figure 1).

Supplementary Table 2. Correlation and statistical significance between gene expression enrichment or depletion and TE enrichment or depletion for 38 histone modifications (refer to Figure 2)

Alu L1 LTR DNA L2 MIRr 0.020132 -0.432517 -0.515575 -0.273047 0.082045 0.194877t 0.120815 -2.878243 -3.610283 -1.702993 0.493936 1.192117p- value 0.461729 0.106439 0.086011 0.169008 0.353964 0.222174

G p G p G p G p G p G p G pH3K4me3 1E+07 0 256505 0 631482 0 43338 0 47430 0 785.51 8E-173 1E+06 0H2BK5ac 1E+06 0 32745 0 93028 0 30925 0 8147.4 0 1084.1 9E-238 328030 0H3K27ac 1E+06 0 70683 0 113936 0 17276 0 7213.2 0 3037.6 0 631482 0H3K9ac 704496 0 25868 0 39591 0 170.19 7E-39 1655.8 0 889.88 2E-195 393172 0H2BK120ac 867104 0 400.38 5E-89 131025 0 13074 0 6183.6 0 3330.9 0 43488 0H4K91ac 825807 0 40683 0 361975 0 3306.9 0 10818 0 5742.5 0 339941 0H3K18ac 839704 0 3948.1 0 277985 0 905.94 5E-199 3900.1 0 11484 0 122161 0H3K4ac 374450 0 233.18 1E-52 104050 0 1532.5 0 2043.1 0 5524.2 0 42598 0H4K5ac 387350 0 52285 0 277515 0 2964.4 0 58.931 2E-14 17378 0 34153 0H2AK5ac 3903.8 0 245.18 3E-55 31759 0 267.37 4E-60 2349.2 0 3721.6 0 52898 0H3K36ac 610986 0 10898 0 83990 0 43.966 3E-11 97.349 6E-23 12808 0 197773 0H2AK9ac 32030 0 521.13 2E-115 1895.2 0 237.85 1E-53 41.383 1E-10 119.29 9E-28 135891 0H2BK20ac 526082 0 38126 0 246447 0 1629.1 0 2537.9 0 12181 0 45170 0H3K79me2 21442 0 89641 0 45170 0 42666 0 6754.8 0 6781.9 0 210506 0H2AZ 1E+06 0 162729 0 210232 0 24984 0 89.998 2E-21 19695 0 40338 0H2BK12ac 178059 0 36576 0 3475.3 0 13799 0 800.01 5E-176 1022.1 3E-224 31.912 2E-08H3K79me3 112140 0 758275 0 210506 0 15433 0 4203.6 0 14.253 0.0002 604264 0H4K8ac 321071 0 5587.4 0 146713 0 95.08 2E-22 443.6 2E-98 12248 0 176401 0H4K12ac 43343 0 794.61 8E-175 23035 0 7388.6 0 3178.8 0 4804.7 0 535117 0H3K4me2 429727 0 133398 0 328030 0 3232.7 0 1351.8 6E-296 7970.3 0 210232 0H3K36me3 755.92 2E-166 547116 0 197773 0 30072 0 436.06 8E-97 397.18 2E-88 104050 0H4K20me1 108316 0 689687 0 604264 0 191451 0 12041 0 2979.5 0 39591 0H3K9me1 316935 0 329307 0 393172 0 1812.2 0 18.433 2E-05 12763 0 42732 0H4K16ac 185657 0 71982 0 173120 0 4358.4 0 2631.7 0 1663.9 0 277985 0H3K23ac 19191 0 1029.7 6E-226 57430 0 15700 0 2106 0 13714 0 57430 0H3K79me1 28992 0 386834 0 135891 0 7202 0 167.13 3E-38 2915.6 0 113936 0H2BK5me1 102758 0 455709 0 535117 0 37498 0 8930.4 0 2481.6 0 83990 0H3K4me1 364966 0 2E+06 0 1E+06 0 55818 0 20559 0 11246 0 277515 0H3K9me3 14451 0 422117 0 339941 0 1078 2E-236 3179.1 0 2838.4 0 146713 0H3K27me1 8759.4 0 163552 0 122161 0 14708 0 972.46 2E-213 5277.9 0 23035 0H3K14ac 3431.7 0 2621.7 0 42732 0 19526 0 646.07 2E-142 6931.8 0 173120 0H3R2me1 4024 0 36426 0 40338 0 15997 0 476.23 1E-105 11191 0 361975 0H4K20me3 2818.1 0 224032 0 176401 0 142879 0 90922 0 95259 0 31759 0H3K36me1 4233.2 0 3358.6 0 52898 0 85314 0 2590.1 0 13606 0 1895.2 0H3K9me2 1330.9 2E-291 23439 0 43488 0 105773 0 2090.8 0 2455.2 0 93028 0H3R2me2 665.8 8E-147 97294 0 31.912 2E-08 734.18 1E-161 513.93 9E-114 3412.1 0 3475.3 0H3K27me3 18.077 2E-05 8247.2 0 34153 0 270665 0 948.08 3E-208 38819 0 246447 0H3K27me2 6453.1 0 11951 0 42598 0 207220 0 18.26 2E-05 4549.8 0 131025 0

L2DNA MIR

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Expression Alu L1 LTR

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Supplementary Figure 3. Comparison of global versus local methods for computing TE-histone modification enrichment ratios. For each TE class (family), log2 normalizedenrichment ratios were computed for the 38 histone modifications by using a genome-wide background tag count (y-axis) or a locally computed background tag count (x-axis).

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Alu L1 LTR DNA L2 MIR

Supplementary Figure 4. Enrichment or depletion of 38 individual histone modificationsin TE families. Log2 normalized ratio of the number of tags of each of the 38 histonemodifications located within each TE family over the local genomic background tag count.TE-modification enrichment values were calculate using the local genomic background histone modification tag counts, which were computed as described in the Methods section.

Supplementary Figure 5. Correlation between enrichment of histone modifications in TE families and for human gene expression. The enrichment of 38 histone modifications in human gene expression (Supplementary Figure 2) is plotted against the same in 6 TE families (Supplementary Figure 1). TE-histone modification enrichment values were calculated using the local genomic background histone modification tag counts, which were computed as described in the Methods section. Pearson correlation coefficient values (r) are shown.

r = -0.56

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Supplementary Figure 6. Enrichment or depletion of active and repressive histone modifications in retrotransposons. Histone modifications were classified as active or repressive based on expression enrichment (Supplementary Figure 1). The log2 normalized ratios of the number of tags of active or repressive modifications located within each family of retrotransposons over the modification background tag counts are shown. Backgroundmodification tag counts were calculate using the local genomic background histone modification tag counts, which were computed as described in the Methods section.Retrotransposon families are arranged according to their relative age. Spearman rank correlations between active and repressive TE-modification enrichments (depletions) and the relative ages of TE families are shown.

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(a) Alu active (b) Alu repressive

Supplementary Figure 7. TE distance from genes versus histone modifications. Distances between TE sequences and the nearest genes are binned in 10kb bins and plotted against the number of histone modification tags mapped to the TE sequence, normalized by its length. Tags are mapped using the new mapping procedure. (Refer to Figure 5)

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Supplementary Table 3. Statistics for distances between Alu and L1 sequences and the nearest genes using uniquely mapped tags (Refer to Figure 5)

active repressiveAlu r -0.38 -0.67

t 4.066878956 8.934549001p-value 4.8184E-05 1.23944E-14

L1 r -0.27 -0.01t 2.775961966 0.098999899p-value 0.003197316 0.460670287

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Supplementary Figure 8. Q-Q plots showing the concordance between the expression fold change and data generated from the theoretical Normal distribution (refer to Figure 2).

Supplementary Table 4. Statistics for correlations between Alu and L1 subfamilies and histone modifications (Refer to Figure 4).

active repressiveAlu subfamilies r 0.94 0.93

t 16.5311 15.1812148p-value 3E-19 5.0865E-18

L1 subfamilies r 0.53 -0.13t 3.75001 -0.7866757p-value 0.00029 0.21817526

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sSupplementary Figure 8 contd. Q-Q plots showing the concordance between the TE enrichment fold change data and data generated from the a theoretical Normal distribution (refer to Figure 2).

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Supplementary Figure 9. Q-Q plots showing the non-concordance of millidiv and tags counts with the data generated from the a theoretical Normal distribution (refer to Figure 4).

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Supplementary Figure 10. Q-Q plots showing the non-concordance of modification tag counts with respect to their distance from human genes with the data generated from the a theoretical Normal distribution (refer to Figure 5).

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Supplementary Figure 11. Age of Alu subfamilies determined by divergence from consensus sequence (refer to Figure 4).

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M4

cL1

P4

dL1

MD

aL1

ME

2z

L1M

3e

L1M

4b

L1M

2b

L1M

DL1

ME

1L1

P4

bL1

ME

3L1

MC

5L1

P4

cL1

ME

2L1

MC

bH

AL1

-3A

_M

EL1

ME

cL1

ME

3A

L1M

CL1

MD

bL1

MC

4L1

M3

cH

AL1

-2a

_M

DL1

ME

fL1

ME

3B

L1M

3b

L1M

C4

aL1

ME

3F

L1M

E3

DL1

M3

de

L1M

E3

EL1

ME

4a

L1M

3d

HA

L1b

L1M

Eb

L1M

Eg

L1M

Ea

L1M

Cc

L1M

E3

CL1

M5

L1M

E5

L1M

Ee

HA

L1L1

M7

L1M

Eg

1L1

M3

aL1

ME

g2

HA

L1N

1_

MD

L1M

Ed

L1M

6

Perc

ent

div

erg

ence

fro

m c

onse

nsu

s se

quence

Supplementary Figure 12. Age of L1 subfamilies determined by divergence from consensus sequence (refer to Figure 4).