KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-Actin	Santa Cruz	sc-147778; RRID: AB_626632
Anti-PRMT5	Abeam	Abeam ab109451; RRID: AB_10863428
Anti-SDMA	Cell signaling	#13222; RRID: AB_2714013
Anti-ADMA	Cell signaling	#13522; RRID: AB_2665370
Anti-PRMT1	Cell signaling	CST #2449; RRID: AB_2237696
Anti-MMA	Cell signaling	#8015; RRID: AB_10891776
Anti-EZH2	Cell signaling	CST #5246; RRID: AB_10694683
Anti- γH2Ax	Cell signalling	CST #9718; RRID: AB_2118009
Biological Samples
AML primary patient samples	Princess Margaret Hospital, Memorial Sloan Kettering Cancer Center, & Weill Cornell College of Medicine	N/A
Chemicals, Peptides, and Recombinant Proteins
GSK3203591	SGC Toronto	https://thesgc.org/chemical-probes/GSK591
MS023	SGC Toronto	https://www.thesgc.org/chemical-probes/MS023
EPZO15666	Tocris	Cat. No. 6516
GSK3368712	GSK	N/A
E7107	H3 Biomedicine Inc.	N/A
I-BRD9	SGC Toronto	https://www.thesgc.org/chemical-probes/l-BRD9
SGC-CBP30	SGC Toronto	https://www.thesgc.org/chemical-probes/CBP30
BI-9564	SGC Toronto	https://www.thesgc.org/chemical-probes/BI-9564
I-CBP112	SGC Toronto	https://www.thesgc.org/chemical-probes/l-CBP112
MS049	SGC Toronto	https://www.thesgc.org/chemical-probes/MS049
UNC0638	SGC Toronto	https://thesgc.org/chemical-probes/UNC0638
SGC707	SGC Toronto	https://www.thesgc.org/chemical-probes/SGC707
GSK484	SGC Toronto	https://www.thesgc.org/chemical-probes/GSK484
10X2	SGC Toronto	https://www.thesgc.org/chemical-probes/IOX2
GSK-J4	SGC Toronto	https://www.thesgc.org/chemical-probes/gskj1
Vorinostat	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 149647-78-9
GSK2 334470	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 1227911-45-6
SGC0946	SGC Toronto	https://www.thesgc.org/chemical-probes/SGC0946
PD0332991	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 827022-32-2
CCT244747	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 1404095-34-6
PF-477736	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 952021-60-2
BMS-265246	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 582315-72-8
Irinotecan	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 100286-90-6
SCH772984	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 942183-80-4
Alitretinoin	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 5300-03-8
CX-4945	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 1009820-21-6
Phenoxodiol	Sigma	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 81267-65-4
5Z-7-oxozeaenol	Cayman chemicals	CAS ${\mathcal{N}}^{\underset{\_}{\text{o}}}$ 253863-19-3
Critical Commercial Assays
Caspase-Glo. 3/7 luminescence assay	Promega	G8090
Cell titer Glo	Promega	G7570
MTS assay	Promega	G3582
PTMScan® Asymmetric Di-Methyl Arginine Motif [adme-R] Kit	Cell Signaling Technologies	Kit #13474
PTMScan® Symmetric Di-Methyl Arginine Motif [sdme-RG] Kit	Cell Signaling Technologies	Kit #13563
PTMScan Mono-Methyl Arginine 13 Motif [mme-RG] Kit	Cell Signaling Technologies	Kit #12235
Deposited Data
RNA-seq data	This paper	GEO:GSE123774
MS-proteomics data	This paper	PRIDE: PXD012007
Experimental Models: Cell Lines
Human: K562 cells	ATCC	CLL-243
Human: THP1 cells	ATCC	TIB-202
Human: M0LM13 cells	DSMZ	ACC 554
Human: U937 cells	ATCC	CRL-1593.2
Human: K562 SRSF2P95H/WT knockin cells	Horizon Discovery	N/A
Human: K562 SF3B1K700E/WT knockin cells	Horizon Discovery	N/A
Human: TF1 cells	ATCC	CRL-2003
Human: 0CI-AML5 cells	DSMZ	ACC 247
Human: F-36P cells	DSMZ	ACC 543
Human: GDM-1 cells	ATCC	CRL-2627
Human: KO52 cells	JCRB	CVCL-1321
Human: HNT34 cells	DSMZ	ACC 600
Human: MonoMac6 cells	DSMZ	ACC 124
Human: 5–16 Cre20 (SRSF2 P95L)	(Chang et al., 2018)	N/A
Human: N-2.12 (isogenic normal)	(Chang et al., 2018)	N/A
Experimental Models: Organisms/Strains
Mice: Srsf2P95H/+	(Kim et al., 2015).	N/A
Mice: MLL-AF9/Vav-cre Srsf2WT/WT	(Kim et al., 2015).	N/A
Mice: MLL-AF9/Vav-cre Srsf2P95H/WT	(Kim et al., 2015).	N/A
Mice: Vav-cre transgenic mice (B6.Cg-Tg(Vav1-icre)A2Kio/J)	The Jackson Laboratory	JAX: 008610
Oligonucleotides
Human EZH2 F	(Lee et al., 2016)	TTTCATG CAACACCC AACACT
Human EZH2 R	(Lee et al., 2016)	CCCTGCTTCCCTATCACTGT
Human ATF2 F	This paper	AGTTACATGTGAATTCTG CCAG G
Human ATF2 R	This paper	CTCAAATG G ACTCG CCAACTC
Human INTS3 F	This paper	ATGCCAAG CTGGCTTTGTTTT
Human INTS3 R	This paper	TCCGACATATGGTTGTCCATCTC
Human TRPT1 F	This paper	GG CCAACCAG G GCCATT
Human TRPT1 R	This paper	ATCACCAG CCAAG GAAAG GG
Human HDAC7 F	This paper	GG AAG AATCCACTG CTCCGA
Human HDAC7 R	This paper	GACTGGG CAAAGTGG AAG GG
Human LEF1 F	This paper	CCACCCATCCCGAGAACATC
Human LEF1 R	This paper	AGG CTTCACGTG CATTAGGT
Anti-sense oligonucleotide SCR	This paper	CGGUGUGUGUAUCAUUCUCUAGUGU
Anti-sense oligonucleotide EZH2	This paper	U GAAU C U U CU G U CCAAAAU CCAACAGGCAAU AUA
sgRNA 1 sequence for EZH2	This paper	TTATCAG AAG G AAATTTCC G
sgRNA 2 sequence for EZH2	This paper	TTATG ATG G GAAAGTACACG
Recombinant DNA
LentiCRISPR v2	N/A	Addgene: 52961
Software and Algorithms
Cytoscape 3.4.0	(Shannon et al., 2003)	https://cytoscape.org/
Reactome Fl	(Wuetal., 2014)	N/A
plogo web application	(O’Shea et al., 2013)	N/A
hmLINKER	(Massignani et al., 2019)	N/A
hmSEEKER	(Massignani et al., 2019)	N/A
Prism 7.0	Graphpad	https://graphpad.com/
lmageJ	NIH	https://irnagej-nih-gov.libproxy1.nus.edu.sg/ij/index.html
STAR	(Dobin et al., 2013)	https://github.com/alexdobin/STAR
HTSeq	(Anders et al., 2(15)	N/A
R	R Core Team	https://www.r-project.org/
Bioconductor	(Huber et al., 2015)	N/A
DESeq2	(Love et al., 2014)	10.18129/B9.bioc.DESeq2
rMATS	(Shen et al., 2014)	http://maseq-mats.sourceforge.net/
ggsashimi	(Garrido-Martin et al., 2018)	https://github.com/guigolab/ggsashimi