KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit monoclonal anti-SIRT6 (clone D8D12)	Cell Signaling Technology	Cat# 12486; RRID: AB_2636969
Mouse monoclonal anti-Flag (clone M2)	Sigma-Aldrich	Cat# F3165; RRID:AB_259529
Mouse monoclonal anti-GST (clone B-14)	Santa Cruz Biotechnology	Cat# sc-138; RRID: AB_627677
Mouse monoclonal anti-GFP (clones 7.1 and 13.1)	Roche	Cat# 11814460001; RRID: AB_390913
Mouse monoclonal anti-PPARA (clone H-2)	Santa Cruz Biotechnology	Cat# sc-398394
Mouse monoclonal anti-Flag-Cy3 (clone M2)	Sigma-Aldrich	Cat# A9594; RRID: AB_439700
Rabbit polyclonal anti-c-Myc-Cy5	Bioss	Cat# bs-0842R-Cy5; RRID: AB_11049406
Mouse monoclonal anti-Cy5 (clone CY5–15)	Sigma-Aldrich	Cat# C1117; RRID: AB_477654
Rabbit polyclonal anti-PDK4	Jeoung et al., 2006	N/A (Custom-produced by Sigma-Genosys)
Rabbit polyclonal anti-phospho-PDH-E1α (Ser293)	Millipore	Cat# AP1062; RRID: AB_10616069
Mouse monoclonal anti-PDH-E1α (clone D-6)	Santa Cruz Biotechnology	Cat# sc-377092; RRID: AB_2716767
Mouse monoclonal anti-alpha-Tubulin (clone B512)	Sigma-Aldrich	Cat# T5168; RRID: AB_477579
Rabbit polyclonal anti-PPARA	Santa Cruz Biotechnology	Cat# sc-9000; RRID: AB_2165737
Rabbit polyclonal anti-phospho-AMPk (Thr172)	Cell Signaling Technology	Cat# 2531; RRID: AB_330330
Rabbit monoclonal anti-AMPK (clone D5A2)	Cell Signaling Technology	Cat# 5831; RRID: AB_10622186
Rabbit polyclonal anti-SREBP2	Abcam	Cat# ab30682; RRID: AB_779079
Rabbit polyclonal anti-H3	Abcam	Cat# ab39655; RRID:AB_732921
Rabbit polyclonal anti-H3K9	Abcam	Cat# ab4441; RRID:AB_2118292
Bacterial Strains
Escherichia coli Bl21 (De3) strain	New England Biolabs	Cat# C2527
Escherichia coli Dh5a strain	Invitrogen	Cat# 18263012
Chemicals, Peptides, and Recombinant Proteins
WY 14643	AbMole	Cat# M1880
Ethidium Bromide	Sigma-Aldrich	Cat# E1510
Carboxymethylcellulose sodium salt	Sigma-Aldrich	Cat# C4888
Formaldehyde 37%	Sigma-Aldrich	Cat# F1635
Collagen	Santa Cruz	Cat# SC-136157
Liver digest medium	Thermo Fisher Scientific	Cat# 17703034
Human Insulin solution	Santa Cruz	Cat# SC-360248
Dexamethasone	Sigma-Aldrich	Cat# D2915
DMSO	Sigma-Aldrich	Cat# D4540
HBSSx10	GIBCO	Cat# 14185045
Sodium Pyruvate	Invitrogen	Cat# 11360–070
Percoll	Sigma-Aldrich	Cat# P1644
EDTA	Santa Cruz	Cat# SC-29092
Dynabeads Protein G	Thermo Fisher Scientific	Cat# 10003D
Medium199	Invitrogen	Cat# 11150–059
Proteinase K	Roche	Cat# 3115879001
TriReagent	Sigma-Aldrich	Cat# 93289
Lipofectamine 2000	Thermo Fisher Scientific	Cat# 11668027
Lipofectamine RNAiMAX	Thermo Fisher Scientific	Cat# 13778075
Flag×3 Peptide	Sigma-Aldrich	Cat# F4799
Critical Commercial Assays
ANTI-FLAG® M2 Affinity Gel	Sigma-Aldrich	Cat# A2220
GFP-Trap Agarose	Chromotek	Cat# gta200
RevertAid First Strand cDNA Synthesis Kit	Thermo Fisher Scientific	Cat# K1621
Agencourt AMPure XP kit	Beckman Coulter	Cat# A63881
NEBNext® Multiplex Oligos for Illumina	New England Biolabs	Cat# E7335
Qubit dsDNA HS Assay Kit	Invitrogen	Cat# Q32851
NEBNext® Ultra DNA Library Prep Kit for Illumina	New England Biolabs	Cat# E7370
NextSeq 500/550 High Output Kit v2.5	Ilumina	Cat# 20024906
Deposited Data
Raw and analyzed RNA sequencing data	This paper	GEO: GSE140063
Mus musculus genome build 38 GRCm38.p6	Ensembl	Mus_musculus.GRCm38.dna.primary_assembly.fa
Experimental Models: Cell Lines
Human HEK293T	ATCC	Cat. # CRL-11268; RRID:CVCL_0063
Mouse Hepa1–6	ATCC	Cat# CRL-1830, RRID:CVCL_0327
Mouse AML12	ATCC	Cat# CRL-2254, RRID:CVCL_0140
Experimental Models: Organisms/Strains
C57B-SIRT6-TG (SIRT6 Overexpression)	Kanfi et. al., 2012	Cohen Lab
CB6-SIRT6-TG (SIRT6 Overexpression)	Kanfi et. al., 2012	Cohen Lab
129-Sirt6tm1Fwa/J (SIRT6 Heterozygote)	The Jackson Laboratory	Kind gift from Dr. Raul Mostoslavsky
Oligonucleotides
Oligonucleotides for Chip	This paper	Table S3, tab A
Oligonucleotides for qRT-PCR	This paper	Table S3, tab B
TriFECTA RNAi Kit for PPARA mouse	IDT	mm.Ri.Ppara.13
Recombinant DNA
pSG5-Ncoa2-Flag	Ogawa et. al., 2004	Kind gift from Dr. Hidesato Ogawa
pSG5-Ncoa2	Leers et. al., 1998	Kind gift from Dr. Hinrich Gronemeyer
pCDNA3.1+-Ncoa2-Flag	This paper	N/A
pCDNA3.1+-Ncoa2K780Q-Flag	This paper	N/A
pCDNA3.1+-Ncoa2K780R-Flag	This paper	N/A
pCAGGS-SIRT6	This paper	N/A
pCAGGS-SIRT6-H133Y	This paper	N/A
pCDNA3.1+-SIRT6-Flag	Gil et. al, 2013	N/A
pCDNA-PPARA-GFP	This paper	N/A
pGEX4t3-GST-PPARA	This paper	N/A
pET28a-His-PPARA	This paper	N/A
pET28a-SIRT6-Flag	Gil et. al, 2013	N/A
Software and Algorithms
ImageJ Version 1.8	Schneider et al., 2012	https://imagej.nih.gov/ij
Bowtie2	Langmead and Salzberg, 2012	http://bowtie-bio.sourceforge.net/bowtie2/index.Shtml
Samtools	Li et al., 2009	http://samtools.sourceforge.net/
STAR 2.6	Dobin and Gingeras, 2015	https://github.com/alexdobin/STAR
MarkDuplicates tool in picard-tools-1.8.4	Broad Institute	http://broadinstitute.github.io/picard/
R (version 3.2.3)	The R Foundation	https://www.r-project.org/
R Studio	The R Foundation	https://rstudio.com/
DESeq2 (version 1.10)	Love et al., 2014	https://bioconductor.org/packages/release/bioc/html/DESeq2.html
GraphPad Prism (version 8.0 for Windows)	GraphPad	https://www.graphpad.com/scientific-software/prism/
Ggplot2	Hadley Wickham	https://ggplot2.tidyverse.org/
Ingenuity Pathway Analysis	QIAGEN	https://www.ingenuity.com
Other
Multi channel cassette pump	Watson Marlow	Cat# 205CA
C96 MicroWellTM Plates	Thermo Fisher Scientific	Cat# 437796
70 μm cell strainer	Corning	Cat# CLS431751