GO term # of genes% PValue

response to extracellular stimulus 50 2.243158 7.35E-06

response to nutrient 35 1.570211 2.79E-05

response to nutrient levels 44 1.973979 4.35E-05

cellular response to stress 99 4.441454 5.22E-05

regulation of apoptosis 132 5.921938 6.07E-05

regulation of programmed cell death 132 5.921938 9.57E-05

regulation of cell death 132 5.921938 1.13E-04

cell cycle 126 5.652759 1.48E-04

response to DNA damage stimulus 69 3.095559 1.57E-04

programmed cell death 103 4.620906 1.59E-04

positive regulation of apoptosis 77 3.454464 1.84E-04

death 118 5.293854 2.10E-04

apoptosis 101 4.53118 2.20E-04

positive regulation of programmed cell death 77 3.454464 2.33E-04

cell death 117 5.248991 2.39E-04

positive regulation of cell death 77 3.454464 2.66E-04

Supplemental Table 1. GO terms of doxorubicin responsive genes reverted by all three siDINo siRNAs.

0

2

4

6

8

10

12

- + - + - + - +

H1299 control H1299 + P53 H1299 + P53V272C

H1299 + P53R273H(dn)

Fo

ld ∆

Do

x/c

trl

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- 16 h 22 h - 16 h 22 h

MDA-MB SW636

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rl DINOCDKN1A

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dox

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0 4 8 12 16 20 24

fold

∆ D

ox/C

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U20S

doxorubicin (hours)

A

B C

Supplementary Figure S1a. RT-PCR of DINO across a time course of DNA damage in U20S cell line.b. RT-PCR of DINO in H1299 p53 null cells complemented with indicated p53 variants.c. RT-PCR of DINO in cancer cell lines with known p53 mutations.

- +

dox

p53

KO

w

ildty

pe

Supplementary Figure S2(A) Genome browser snapshot of 3-seq in wildtype or p53 null MEFs +/- doxorubicin. Red box indicates region syntenic to human DINO. (B) Genomic context of zebrafish CDKN1A. Grey bars indicate PCR primer amplicons.(C) RT-PCR of TP53 and CDKN1A in zebrafish embryos treated with UV at 18 hpf and harvested at 24 hpf. (D) RT-PCR of regions along the zebrafish CDKN1A promoter +/- UV. Letters correspond to grey bars in (B).

PhastCons Fish Conservation

1 _

0 _

500 bp

zebrafish CDKN1A

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zebrafish CDKN1A

zebrafish TP53

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k j i h g f e d c b a

zDINO

C

-+-+-+

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+

mouse CDKN1A

Inpu

tIP

-IgG

IP-p

53

p53LSD1

MDM2SET7

WB:

Supplementary Figure S4Immunoprecipitation of p53 followed by western blot of known interacting proteins LSD1 and MDM2. Identical conditions did not detect SET7.

00.0050.01

0.0150.02

0.0250.03

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0.0450.05

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00.010.020.030.040.050.060.070.080.090.1

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RRM2b

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aliz

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xpre

ssio

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DDB2

Supplementary Figure S5293 Cells transfected with vector, DINO, or two DINO fragments (0-300 and 450-951) missing the CLIP hairpin. RT-PCR for p53 target genes

SET7

DINO LACZ

lysine methyl

silver stainSET7TAF10

Supplementary Figure S3Under identical enzyme/substrate/RNA conditions as Fig. 3G, no TAF10 methylation was detectable via anti lysine methyl antibody (Abcam Ab23366) (detects TAF10 methylation in Antigone, 2004) or anti pan-methyl Lysine antibody (Abcam Ab7315).

siCTRL siSET7

- + - +SET7

B-actin

02468

10121416

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siCTRL siSET7

Rela

tive

expr

essi

on

CDKN1A

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TP53a b

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siCTRL siSET7

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ativ

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SET7c

dox dox dox

dox dox dox

Supplementary Figure S6a. Western blot of knockdown by SET7 siRNA in U20S cells. b. RT-PCR of indicated genes in U20S cellsc. RT-PCR of indicated genes in primary human fibroblasts