REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Mouse anti-IgG	Santa Cruz	sc2025; RRID:AB_737182
Rabbit anti-H3K4me1	Active Motif	39297; RRID:AB_2615075
Mouse anti-H3K4me3	Active Motif	61379; RRID:AB_2793611
Mouse anti-H3K27me3	Active Motif	61017; RRID:AB_2614987
Mouse anti-H3K27ac	Active Motif	39685; RRID:AB_2793305
Rabbit anti-H3K9ac	Abcam	ab4441; RRID:AB_2118292
Rabbit anti-H3	Abcam	ab1791; RRID:AB_302613
Goat anti-rabbit HRP-conjugated	Sigma	A9169; RRID:AB_258434
Rabbit anti-mouse HRP-conjugated	Sigma	A9044; RRID:AB_258431
Biological samples
Human islets	ECIT Islet for Basic Research program	https://ecit.dri-sanraffaele.org
Chemicals, peptides, and recombinant proteins
Trichostatin A	Sigma	T1952-200UL
Critical commercial assays
BCA assay	Pierce	23227
ECL kit	Pierce	34076
Mouse insulin kit	Mercodia	10-1247-01
Human insulin kit	Mercodia	10-1113-01
RNeasy plus mini kit	Qiagen	74134
RNeasy plus micro kit	Qiagen	74034
TruSeq Stranded mRNA library prep	Illumina	20020594
Nextflex rapid DNA seq kit 2.0	Perkin Elmer	NOVA-5188-01
Transcriptor universal cDNA master	Roche	05893151001
Transcriptase inverse SuperScript™ III	Invitrogen	18080093
FastStart SYBR Green Master	Roche	FSSGMMRO
Deposited data
Raw and analyzed data	This paper	GEO: GSE234144 and GSE234148
The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes	Lu TT et al.17	GEO: GSE110648
Experimental models: Cell lines
Min6	AddexBio	C0018008; RRID:CVCL_0431
EndoC-βH1	Human Cell Design	https://www.humancelldesign.com/human-beta-cells-endoc-bh1/; RRID:CVCL_L909
Experimental models: Organisms/strains
C57Bl6/J	Charles River Laboratories	000664
LSL-Td-Tomato	The Jackson Laboratory	007905
Rip-cre	Herrera, P.L. et al.39	RRID: MGI:6195021
Oligonucleotides
Cyclo_Mm_F	ATGGCACTGGCGGCAGGTCC
Cyclo_Mm_R	TTGCCATTCCTGGACCCAAA
Pdx1_Mm_F	ATTGTGCGGTGACCTCGGGC
Pdx1_Mm_R	GATGCTGGAGGGCTGTGGCG
Mafa_Mm_F	TCCGACTGAAACAGAAGCGG
Mafa_Mm_R	CTCTGGAGCTGGCACTTCTC
Foxo1_Mm_F	TGCCCAACCAAAGCTTCCCACA
Foxo1_Mm_R	TGGACTGCTCCTCAGTTCCTGCT
Ins1_Mm_F	GCCAAACAGCAAAGTCCAGG
Ins1_Mm_R	GTTGAAACAATGACCTGCTTGC
Software and algorithms
GSEA	Subramanian et al.40; Mootha et al.41	http://www.broadinstitute.org/gsea/; RRID:SCR_003199
Metascape	Zhou et al.42	http://metascape.org/gp/index.html#/main/step1; RRID:SCR_016620
GREAT	McLean et al.16	http://great.stanford.edu/public/html/splash.php; RRID:SCR_005807
Ingenuity Pathway Analysis	Qiagen	http://www.ingenuity.com/products/pathways_analysis.html; RRID:SCR_008653
Bcl2fastq conversion software	Illumina	https://support.illumina.com/sequencing/sequencing_software/bcl2fastq-conversion-software.html; version 2.19.1 and version 2.20; RRID:SCR_015058
Cutadapt	http://code.google.com/p/cutadapt/	version 1.7.1; RRID:SCR_011841
STAR	http://code.google.com/p/rna-star/	version 2.5.2b; RRID:SCR_004463
RSEM	http://deweylab.biostat.wisc.edu/rsem/	version 1.3; RRID:SCR_013027
DEseq2	https://bioconductor.org/packages/release/bioc/html/DESeq2.html	RRID:SCR_015687
Trim Galore	http://www.bioinformatics.babraham.ac.uk/projects/trim_galore/	version 0.4.5; RRID:SCR_011847
Bowtie2	http://bowtie-bio.sourceforge.net/bowtie2/index.shtml	version 2.3.5.1; RRID:SCR_016368
MACS2	https://github.com/macs3-project/MACS	RRID:SCR_013291
GraphPad Prism 9.0	GraphPad	RRID:SCR_002798