REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
FITC anti-mouse CD4	Biolegend	Cat# 130308, RRID: AB_1279237
APC anti-mouse CD8a	Biolegend	Cat# 100711, RRID: AB_312750
Brilliant Violet 785™ anti-mouse CD45	Biolegend	Cat# 103149, RRID: AB_2564590
PE anti-mouse CD62L	Biolegend	Cat# 104407, RRID: AB_313094
APC anti-mouse CD44	Biolegend	Cat# 103012, RRID: AB_312963
PE/Cy7 anti-mouse IL-17A	Biolegend	Cat# 506922, RRID: AB_2125010
Pacific Blue™ anti-mouse IFN-γ	Biolegend	Cat# 505818, RRID: AB_893526
APC anti-mouse IL-4	Biolegend	Cat# 504106, RRID: AB_315320
PE/Cy7 anti-mouse CD11b	Biolegend	Cat# 101216, RRID: AB_312799
PerCP/Cyanine5.5 anti-mouse CD3	Biolegend	Cat# 100217, RRID: AB_1595597
PE anti-mouse CD170 (Siglec-F)	Biolegend	Cat# 155506, RRID: AB_2750235
APC anti-mouse F4/80	Biolegend	Cat# 123116, RRID: AB_893481
APC/Fire™ 750 anti-mouse Ly-6C	Biolegend	Cat# 128045, RRID: AB_2616730
Brilliant Violet 421™ anti-mouse I-A/I-E (MHC-II)	Biolegend	Cat# 107631, RRID: AB_10900075
FITC anti-mouse Ly-6G	Biolegend	Cat# 127606, RRID: AB_1236494
APC anti-mouse CD11c	ThermoFisher	Cat# 17-0114-81, RRID: AB_469345
APC anti-mouse FOXP3	ThermoFisher	Cat# 77-5775-40, RRID: AB_469981
PE anti-mouse CD45RB	Biolegend	Cat# 103308, RRID: AB_313015
anti-mouse CD3ε	Bio X Cell	Cat# BE0001-1, RRID: AB_1107634
anti-mouse CD28	Bio X Cell	Cat# BE0015-5, RRID: AB_1107628
anti-mouse IFNγ	Bio X Cell	Cat# BE0055, RRID: AB_1107694
anti-pSTAT4	R and D Systems	Cat# PA-ST4, RRID: AB_2302639
anti-STAT4	R and D Systems	Cat# MAB5287, RRID: AB_2302638
anti-H3	Abcam	Cat# 10799, RRID: AB_470239
anti-H3K4me1	Abcam	Cat# ab8895, RRID: AB_306847
anti-H3K4me3	Millipore	Cat# 17-614, RRID: AB_11212770
anti-H3K27ac	Abcam	Cat# ab4729, RRID: AB_2118291
anti-GATA3	BD bioscience	Cat# 558686, RRID: AB_2108590
anti-T-bet	BD bioscience	Cat# 561263, RRID: AB_10563082
anti-MLL4	1	N/A
Bacterial strains
Listeria monocytogenes	ATCC	Cat# 35152™
Chemicals, peptides, and recombinant proteins
House Dust mite protein	Greer Laboratories	Cat# XPB82D3A2.5
LB Broth	Sigma	Cat# L3522
LB Broth with agar	Sigma	Cat# L3147
PMA	Sigma	Cat# P8139
Ionomycin	Sigma	Cat# I0634
Recombinant Human TGF-beta 1 Protein	R&D	Cat# 240-B-002
Recombinant Mouse IL-12 Protein	R&D	Cat# 419-ML-010
Recombinant Mouse IL-4 Protein	R&D	Cat# 404-ML-010
Recombinant Mouse IL-6 Protein	R&D	Cat# 406-ML-005
formaldehyde	Thermo Scientific	Cat# 28908
T4 DNA polymerase	New England Biolabs	Cat#M0203L
rCutSmart buffer	New England Biolabs	Cat# B6004S
Hpa I	New England Biolabs	Cat# R0105L
MluCI	New England Biolabs	Cat# R0538L
NlaIII	New England Biolabs	Cat# R0125L
Proteinase K	Roche	Cat# 03115828001
T4 DNA Ligase	New England Biolabs	Cat# M0202L
Critical commercial assays
ELISA MAX™ Standard Set Mouse IFN-γ	Biolegend	Cat# 430801
Mouse IgE ELISA MAX™ Deluxe	Biolegend	Cat# 432404
Fixation/Permeabilization Solution Kit with GolgiPlug™	BD Biosciences	Cat# 555028
Foxp3 / Transcription Factor Fixation/Permeabilization Concentrate and Diluent	ThermoFisher	Cat# 00-5521-00
iScript RT Supermix for RT-qPCR	Biorad	Cat# 1708841
RNeasy Plus Mini Kit	Qiagen	Cat# 74136
End-It DNA-Repair kit	Epicentre	Cat#ER0720
Deposited data
Hi-C data from wild-type and MLL4 KO mice naïve CD4+ cells	2	GEO accession#: GSE69162
MLL4 and H3K4me1 ChIP-seq data from wild-type and MLL4 KO mice naïve CD4+ cells	2	GEO accession#: GSE69162
GATA3 ChIP-seq data from mice Th1 cells	3	SRA accession#: SRR038548
T-bet ChIP-seq data from mice Th1 cells	4	SRA accession#: SRR372732
H3K4me1 ChIP-seq data from human Jurkat cells	5	GEO accession#: GSM1603224
GATA3 ChIP-seq data from human Jurkat cells	6	GEO accession#: GSE68976
RNA-seq	This paper	GEO accession#: GSE204946
ChIP-seq	This paper	GEO accession#: GSE204946
Hi-TrAC	This paper	GEO accession#: GSE204946
Experimental models: Organisms/strains
Mouse: Mll4fl/fl	1	N/A
Mouse: CD4cre	Taconic	Model#4196
Mouse: hCD2Cre	(Gurram et al., 2023)	N/A
Mouse: Gata3fl/fl	(Gurram et al., 2023)	N/A
Mouse: G28∆	This paper	N/A
Mouse: CNS-28∆	This paper	N/A
Oligonucleotides
CNS–28∆ sgRNA-1: ATTAAGACCTCGTTGAAGGC	IDT	N/A
CNS–28∆ sgRNA-2: GAGATCTTATCATGCCGTCT	IDT	N/A
G28∆ sgRNA-1: AATTAAGTCTTAACAGAAGG	IDT	N/A
G28∆ sgRNA-2: ACTCTGCATGGTTCCCATT	IDT	N/A
Cas9 mRNA	TriLink Biotechnologies	L-6125
CNS-22/F: ACCTGCACTTCTGTGAGCACAT	IDT	N/A
CNS-22/R: AGGCGCTGACATCATGCTT	IDT	N/A
CNS-22/Probe: CACGCATCGCCCCGCCCTAT	IDT	N/A
CNS-28/F: GTTGAAGGCAGGTACTGTGATA	IDT	N/A
CNS-28/R: CCATCCTAGACGGCATGATAAG	IDT	N/A
CNS-28/Probe: ACTCATGTCCATGTGCTA	IDT	N/A
CNS+41/F: GCAAAGGCTCAGACTGAAGATA	IDT	N/A
CNS+41/R: ACAGAGTTTCTGGAGAGAGTAGA	IDT	N/A
CNS+41/Probe: CGGAGTCAGAAGCAGGGTTACAGC	IDT	N/A
Ifng promoter/F: CAGCCGTCCCCAACCA	IDT	N/A
Ifng promoter/R: GCCCTTGTAATGTGAATTTCTCATC	IDT	N/A
Ifng promoter/Probe: CAAAGGCTCCCTGTGCTGTGCTCTG	IDT	N/A
Foxp3 probe	ThermoFisher	Mm00475162
Ifng probe	ThermoFisher	Mm01168134
Tbx21 probe	ThermoFisher	Mm00450960
Gata3 probe	ThermoFisher	Mm00484683
Il4 probe	ThermoFisher	Mm00445259
Il5 probe	ThermoFisher	Mm00439646
Il13 probe	ThermoFisher	Mm00434204
Actb probe	ThermoFisher	4352341E
Software and algorithms
GraphPad Prism version 8 for MacOS	Graphpad Software	https://www.graphpad.com
FlowJo	TreeStar	https://www.flowjo.com/
Python (v3)	Python Community	https://www.python.org
seaborn (v0.11.0)	7	https://seaborn.pydata.org
Bowtie2 (v.2.3.5)	8	https://bowtie-bio.sourceforge.net/bowtie2/index.shtml
STAR (v2.7.3a)	9	https://github.com/alexdobin/STAR
Cuffdiff (v2.2.1)	10	https://github.com/cole-trapnell-lab/cufflinks
deepTools2 (v3.3.0)	11	https://deeptools.readthedocs.io/en/develop/
HiC-Pro (v2.11.1)	12	https://github.com/nservant/HiC-Pro
Juicer (v1.11.04)	13	https://github.com/aidenlab/juicer
cLoops2 (v0.0.3)	14	https://github.com/YaqiangCao/cLoops2
HOMER (v4.10.4)	15	http://homer.ucsd.edu/homer/
Other