REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
H3K27me3 C36B11	Cell Signaling Technology	Cat No. 9733S; RRID: AB_2616029
Total H3	Abcam	Cat No. Ab1791; RRID: AB_302613
H3K4me3 C42D8	Cell Signaling Technology	Cat No. 9751S; RRID: AB_2616028
Histone H3 (tri methyl K36) antibody - ChIP Grade	Abcam	Cat No. ab9050; RRID: AB_306966
Anti-Histone H3 (tri methyl K79) antibody - ChIP Grade, purified	Abcam	Cat No. ab195500
Chemicals, Peptides, and Recombinant Proteins
DMEM	Thermo Fisher Scientific	Cat No. 11965092
FBS	Invitrogen	Cat No. 26400-036
Shields and Sang M3 insect medium	Sigma-Aldrich	Cat No. S8398
EdU	Invitrogen	Cat No. A10044
Biotin-16-dUTP	IBA oligonucleotides	N/A
Biotin-TEG-Azide	Berry & Associates	Cat No. BT1085
Free Biotin	Sigma-Aldrich	Cat No. B4501
THPTA	Sigma-Aldrich	Cat No. 762342
Aminoguanidine hydrochloride	Sigma-Aldrich	Cat No. 396494
Protein A agarose beads	Thermo Fisher Scientific	Cat No. 20333
Dynabeads MyOne Streptavidin T1	Thermo Fisher Scientific	Cat No. 65602
EPZ-6438 EZH2 inhibitor	Selleckchem	Cat No.S7128
Agencourt AMPure XP	Beckman Coulter	Cat No. A63880
Critical Commercial Assays
Click-IT Alexa Fluor 488 imaging kit	Thermo Fisher Scientific	Cat No. C10337
QIAGEN MiniElute PCR purification kit	QIAGEN	Cat No. 28004
NEB Next Ultra DNA Library prep kit	New England Biolabs	Cat No. NEB E7370S
KAPA Hyperprep Kit	Kappa Biosystems, Roche	Cat No. KK8504
Deposited Data
Repli-seq	ENCODE Project Consortium, 2012	GEO: GSM923449
Encode HeLa S3 H3K27me3 ChIP	Bernstein et al., 2005	GEO: GSM733696
Encode HeLa S3 H3K4me3 ChIP	Bernstein et al., 2005	GEO: GSM733682
HeLa S3 EZH2 ChIP	Bernstein et al., 2005	GEO: GSM1003520
HeLa S3 RNaseq	Mortazavi et al., 2008	GEO: GSM958735
HeLa H3.3 ChIP	Ray-Gallet et al., 2011	GEO: GSM788633
TSSs	http://hgdownload.soe.ucsc.edu/goldenPath/hg19/encodeDCC/wgEncodeCaltechRnaSeq/	wgEncodeCaltechRnaSeqHelas3R2x75Il200TSSRep1V3.gtf.gz
RefSeq	http://hgdownload.soe.ucsc.edu/goldenPath/hg19/database/	refGene.txt.gz
CpG densities	Illingworth et al., 2010	https://doi.org/10.1371/journal.pgen.1001134.s001
Raw and analyzed data	This paper	GEO: GSE110354
Experimental Models: Cell lines
Human HeLa S3 cells	ATCC	Cat. No. CCL-2-2; RRID: CVCL_0058
Drosophila S2-DRSC cells	Drosophila Genomics Resource Center; Stock No. 181	RRID: CVCL_Z992
Oligonucleotides
NGS indexed PentAdapters	PentaBase	Cat No. SKU 310
Software and Algorithms
Bowtie 1	Langmead et al., 2009	http://bowtie-bio.sourceforge.net/index.shtml
Galaxy	Afgan et al., 2016	RRID: SCR_006281; https://galaxyproject.org/
MACS	Zhang et al., 2008	http://liulab.dfci.harvard.edu/MACS/
R v.3.2.1	Huber et al., 2015	https://www.bioconductor.org/
SeqPlots v.1	Stempor and Ahringer, 2016	https://bioconductor.org/packages/release/bioc/html/seqplots.html
Hilbertvis v.3.6	Anders, 2009	RRID: SCR_007862; https://bioconductor.org/packages/release/bioc/html/HilbertVis.html