REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
L3MBTL2	Biorbyt	Cat#: orb411730; RRID: AB_10932814
CGA (HCG Alpha Polyclonal Antibody)	Proteintech	Cat#: 25014-1-AP
TP53INP2	Abcam	Cat#: ab273012
ATG7	Abcam	Cat#: ab52472
LC3B	Abcam	Cat#: ab192890; RRID: AB_2827794
SQSTM1/p62	Cell Signaling Technology	Cat#: 5114S; RRID: AB_10624872
mTOR	Cell Signaling Technology	Cat#: 2983S; RRID: AB_2105622
p-mTOR	Cell Signaling Technology	Cat#: 5536S; RRID: AB_10691552
AKT	Cell Signaling Technology	Cat#: 4685S; RRID: AB_2225340
p-AKT	Cell Signaling Technology	Cat#: 4060S; RRID: AB_2315049
GAPDH	Cell Signaling Technology	Cat#: 5174S; RRID: AB_10622025
Beta-Actin	Biorbyt	Cat#: orb181785
H2AK119ub1	Cell Signaling Technology	Cat#: 8240S; RRID: AB_10891618
H3K27me3	Active-Motif	Cat#: 39055; RRID: AB_2561020
HDAC1	Active-Motif	Cat#: 40967; RRID: AB_2614948
H3K9me3	Active-Motif	Cat#: 39065; RRID: AB_2793334
H3K36me3	Active-Motif	Cat#: 61902; RRID: AB_2615073
Goat Anti-Rabbit IgG antibody (HRP)	Biorbyt	Cat#: orb43514; RRID: AB_10998428
Goat Anti-Mouse IgG(H+L) antibody (HRP)	Biorbyt	Cat#: orb506151
Rabbit mAb IgG	Cell Signaling Technology	Cat#: 66362
Chemicals, peptides, and recombinant proteins
RPMI-1640	Gibco	Cat#: A1049101
DMEM	Gibco	Cat#: 11995040
EBSS	Gibco	Cat#: 14155063
Fetal bovine serum (FBS)	Gibco	Cat#: 10099141
PBS	Gibco	Cat#: 70011-044
Streptomycin reagent	Hyclone	Cat#: SV30010
Penicillin	Hyclone	Cat#: SV30010
TRIzol Reagent	Invitrogen	Cat#: 15596026
Cell lysis buffer	Beyotime	Cat#: P0013
Protease and phosphatase inhibitor cocktail	Beyotime	Cat#: P1050
RIPA	Beyotime	Cat#: P0013B
Crystal violet	Sigma	Cat#: C6158
pentobarbital sodium	Sigma	Cat#: P3761
Rapamycin	MedChemExpress	Cat#: HY-10219
Skim milk	BD	Cat#: 232100
Critical commercial assays
HiScript III 1st Strand cDNA Synthesis Kit	Vazyme	Cat#: R312-01/02
ChamQ SYBR Color qPCR Master Mix	Vazyme	Cat#: Q411-02/03
BeyoECL Moon super sensitivity detection kit	Beyotime	Cat#: P0018FS
Chromatin IP DNA Purification Kit	Active Motif	Cat#: 58002
CUT&RUN Assay Kit	Cell Signaling Technology	Cat#: 86652
Cell Counting Kit-8	Solarbio	Cat#: CK04
Deposited data
Raw and analyzed RNA sequencing data	This paper	GEO: GSE184834
Experimental models: Cell lines
Human: PANC-1	ATCC	Cat#: CRL-1469
Human: ASPC-1	ATCC	Cat#: CRL-1682
Human: BXPC-3	ATCC	Cat#: CRL-1687
Human: HPDE6-C7	ATCC	RRID: CVCL_0P38
Human: H1299	ATCC	Cat#: CRL-5803
Human: HepG2	ATCC	Cat#: HB-8065
Experimental models: Organisms/strains
Mouse: BALB/c nude mice (6-week-old, female)	Charles River	Cat# 401
Oligonucleotides
Sh L3MBTL2-1 5’- GCTTCGGTATGAAGGCTTTGAA-3’	This paper	N/A
Sh L3MBTL2-2 5’- GCGTGTGAAGGAAGAGCATCTA-3’	This paper	N/A
Sh CGA-1 5’- CCACTGCAGTACTTGTTATTA -3’	This paper	N/A
si-CGB	Thermo Fisher Scientific	Cat#: 247166
si-LHB	Thermo Fisher Scientific	Cat#: 214223
si-TSHB	Thermo Fisher Scientific	Cat#: 138744
si-FSHB	Thermo Fisher Scientific	Cat#: 144547
RT-PCR primers (Table S1)	This paper	N/A
CGA-promotor-sgRNA1 5’-CATGGTAAAAATTGACGTCA-3’	This paper	N/A
CGA-promotor-sgRNA2 5’- ACCAAGTACCCTTCAATCAT- 3’	This paper	N/A
CGA-promotor-sgRNA3 5’- TGATCCCAGGGCTTAGATGC-3’	This paper	N/A
Recombinant DNA
pCDH-EF1α-MCS-T2A-Puro	System Biosciences	CD527A-1
pLVX-shRNA2	Clonetech	632179
pGL4.11	Promega	E6661
pcDNA3.1	Thermo Fisher Scientific	V79520
pLVX-TetONE-Puro	Takara	631849
dxCas(3.7)-VPR	Addgene	108383
ptfLC3	Addgene	21074
pEF-PUP-IT (pupylation-based interaction tagging) proximity-tagging system	(Liu et al., 2018b)	N/A
pLVX-Pup(E)-TET-ONE	This paper	N/A
pGL4-CGApromoter	This paper	N/A
pcDNA3.1-dxCas9(3.7)-PafA	This paper	N/A
pcDNA3.1-LC3B-PafA-IRES-PupE	This paper	N/A
pcDNA3.1-dCas9-USP16	This paper	N/A
pcDNA3.1-dCas9-KDM6B	This paper	N/A
pcDNA3.1-dCas9-HDAC3	This paper	N/A
pcDNA3.1-dCas9-EP300	This paper	N/A
Software and algorithms
Prism8	GraphPad	https://www.graphpad.com/scientific-software/prism/
SnapGene 4.3	SnapGene	https://www.snapgene.com