REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-MeCP2 antibody, mouse monoclonal, clone Men-8	Sigma	Cat#M7443 Lot 125M4851; RRID:AB_477235
Anti-MeCP2 antibody, mouse monoclonal, clone Mec-168	Sigma	Cat#M6818 RRID:AB_262075
Anti-GFP antibody, rabbit monoclonal, clone D5.1	New England Biolabs	Cat#2956 Lot 4; RRID: AB_1196615
Anti-NCOR1 antibody, rabbit polyclonal	Bethyl	Cat# A301-146A; RRID: AB_873086
Anti-TBL1XR1 antibody, mouse monoclonal	Santa Cruz	Cat# sc-100908; RRID: AB_1130006
Anti-HDAC3 antibody, mouse monoclonal, clone 3E11	Sigma	Cat# WH0008841M2 Lot D3011-3E11; RRID: AB_1841895
Anti-Histone H3 antibody, rabbit polyclonal	Abcam	Cat#ab1791 Lot GR242682-2; RRID: AB_302613
Anti-NeuN Antibody, clone A60	Millipore	Cat#MAB377 Lot NG1876252; RRID:AB_2298772
Anti-NeuN Antibody, clone A60, Cy3 Conjugate	Millipore	Cat#MAB377C3; RRID: AB_10918200
IRDye® 800CW Donkey anti-Mouse	LI-COR	Cat#926-32212; RRID: AB_621847
IRDye® 800CW Donkey anti-Rabbit	LI-COR	Cat#926-32213; RRID: AB_621848
IRDye® 680LT Donkey anti-Rabbit	LI-COR	Cat#926-68023; RRID:AB_10706167
Sheep Anti-Mouse IgG - HRP Conjugated	GE Healthcare	Cat#NA931; RRID: AB_772210
Donkey Anti-Rabbit IgG, HRP Conjugated	GE Healthcare	Cat#NA934; RRID: AB_772206
Bacterial and virus strains
BL21(DE3)RIPL	Agilent	Cat#230280
BL21(DE3)-R3- pRARE2	Oxford Structural Genomic Consortium (SGC); Savitsky et al., 2010	N/A
BL21(DE3)pLysS	Promega	Cat#L119B
Chemicals, peptides, and recombinant proteins
MeCP2 77-167, mouse	This manuscript	N/A
MBD2 139-224, human	This manuscript	N/A
MeCP2 N-term, mouse	This manuscript	N/A
MM2 N-term, derived from mouse MeCP2 and MBD2	This manuscript	N/A
Critical commercial assays
GFP-Trap®_A beads for protein pulldown	Chromotek	Cat#gta
Puregene Core Kit A	QIAGEN	Cat#1042601
Deposited data
RettBASE: RettSyndrome.org Variation Database	Krishnaraj et al., 2017	http://mecp2.chw.edu.au
Whole genome bisulphite sequencing, mouse hypothalamus	Lagger et al., 2017	GEO: GSE84533
ATAC-seq and RNA-seq data	This manuscript	GEO: GSE152801
Independent hypothalamus RNA-seq (Mecp2-null versus WT)	Chen et al., 2015	GEO: GSE66870
Cortex RNA-seq (Mecp2-null versus WT)	Boxer et al., 2019	GEO: GSE128178
All Mendeley data	This manuscript	http://DOI.org/10.17632/4bj84x6kcy.1
Experimental models: cell lines
mESC, MM2 knockin, clone 5C7	This manuscript	N/A
E14 TG2a ES cells (derived from 129/Ola male mouse embryo)	Andrew Smith at the Centre for Genome Research (now Institute for Stem Cell Research), University of Edinburgh	N/A
HeLa	Bird lab	N/A
NIH 3T3	ATCC	RRID:CVCL_0594
Experimental models: organisms/strains
Mouse: WT-EGFP: C57BL/6J-Mecp2tm3.1Bird	Brown et al., 2016	RRID: IMSR_JAX:014610
Mouse: MM2-EGFP: C57BL/6J-Mecp2em7.1Bird	This manuscript	N/A
Mouse: Mecp2-null: C57BL/6J.CBA/CA-Mecp2tm2Bird	Guy et al., 2001	RRID: IMSR_JAX:006849
Mouse: CMV-Cre; C57BL/6J- Tg(CMV-cre)1Cgn	Schwenk et al., 1995	RRID: IMSR_JAX:006054
Mouse: T158M-EGFP: C57BL/6J-Mecp2tm4.1Bird	Brown et al., 2016	RRID:IMSR_JAX:026762
Mouse: R306C-EGFP: C57BL/6J-Mecp2tm5.1Bird	Brown et al., 2016	RRID:IMSR_JAX:026847
Mouse: R133C-EGFP: C57BL/6J-Mecp2tm6.1Bird	Brown et al., 2016	RRID:IMSR_JAX:026848
Oligonucleotides
See Table S4 for primer sequences	N/A	N/A
BLI probes (methylated C is underlined): CG sense: 5′-Bio-TCTGGAACGGAATTCTTCTA-3′	Integrated DNA Technologies (IDT)	N/A
CG antisense: 5′-ATAGAAGAATTCCGTTCCAG-3′	IDT	N/A
CAC sense: 5′-Bio-TCTGGAACACAATTCTTCTA-3′	IDT	N/A
CAC antisense: 5′-ATAGAAGAATTGTGTTCCAG-3′	IDT	N/A
CAT sense: 5′-Bio-TCTGGAACATAATTCTTCTA-3′	IDT	N/A
CAT antisense: 5′-ATAGAAGAATTATGTTCCAG-3′	IDT	N/A
MBD2[MBD] EMSA probes (methylated C is underlined) CG sense: 5′-FAM-TCTGGAACGGAATTCTTCTA-3′	IDT	N/A
CG antisense: 5′-ATAGAAGAATTCCGTTCCAG-3′	IDT	N/A
CAC sense: 5′-FAM-TCTGGAACACAATTCTTCTA-3′	IDT	N/A
CAC antisense: 5′-ATAGAAGAATTGTGTTCCAG-3′	IDT	N/A
CAT sense: 5′-FAM-TCTGGAACATAATTCTTCTA-3′	IDT	N/A
CAT antisense: 5′-ATAGAAGAATTATGTTCCAG-3′	IDT	N/A
N-term EMSA probes (methylated C is underlined): CG sense: 5′-AAGCATGCAATGCCCTGGAACGGAATTC TTCTAATAAAAGATGTATCATTTTAAATGC-3′	Biomers, Germany; Lagger et al., 2017	N/A
CG antisense: 5′-GCATTTAAAATGATACATCTTTTA TTAGAAGAATTCCGTTCCAGGGCATTGCATGCTT-3′	Biomers, Germany; Lagger et al., 2017	N/A
CAC sense: 5′-AAGCATGCAATGCCCTGGAACACAATTC TTCTAATAAAAGATGTATCATTTTAAATGC-3′	Biomers, Germany; Lagger et al., 2017	N/A
CAC antisense: 5′- GCATTTAAAATGATACATCTTTTA TTAGAAGAATTGTGTTCCAGGGCATTGCATGCTT-3′	Biomers, Germany; Lagger et al., 2017	N/A
Oligos for DNA pull down assay (all Cs are methylated): CG probe: 5′-ACGTATATACGATTTACGTTATACGATT ACGATATACGATTTA CGTTAATACGTTTACGATTATT ACGAATTTACGTTTTTACGAATATACGAAATACGTTT AATACGTAATTACGTATATTACGTATATACGATTTAC GAATTACG-3′	PCR-generated; Connelly et al., 2020	N/A
CAC probe: 5′-GCACACACGCACTTTGCACTATGC ACTTGCACTATGCACTTTG CACTAATGCACTTGCA CTTATTGCACACTTGCACTTTTGCACACACGCACA ATGCACTTAATGCACAATTGCACACACTGCACACA CGCACTTTGCACACTGCA-3′	PCR-generated; This manuscript	N/A
CAT probe: 5′-GCATATATGCATTTTGCATTATGC ATTTG CATTATGCATTTTGCATTAATGCATTTGC ATTTATTGCATATTTGCATTTTTGCATATATGCA TAATGCATTTAATGCATAATTGCATATATTGCAT ATATGCATTTTGCATATTGCA-3′	PCR-generated; This manuscript	N/A
Recombinant DNA
pET28_MeCP2[MBD]	SK lab	N/A
pNIC28-Bsa4_MBD2[MBD]	This manuscript	N/A
MM2 fragment for cloning (PstI sites underlined): 5′-CCACCATTCTGCAGAGCCAGCAGAGGCAGGCAA AGCAGAA ACATCAGAAAGCTCAGGCTCTGCCCC AGCAGTGCCAGAAGCCTCGGCTTCCCCCAAACA GCGGCGCTCCATTATCCGTGACCGGGGACCTAT GGACTGCCCGGCCCTCCCCCCCGGATGGAAGA AGGAGGAAGTGATCCGAAAATCAGGGCTCAGTGC TGGCAAGAGCGATGTCTACTACTTCAGTCCAAGT GGTAAGAAGTTCAGAAGTAAACCTCAGCTGGCAA GATACCTGGGAAATGCTGTTGACCTTAGCAGTTT TGACTTCAGGACCGGCAAGATGATGCC TTCCAGGAGAGAGCAGAAACCACCTAAGAAGCC CAAATCTCCCAAAGCTCCAGGAACTGGCAGGGG TCGGGGACGCCCCAAAGGGAGCGGCAC TGGGAGACCAAAGGCAGCAGCATCAGAAGGTG TTCAGGTGAAAAGGGTCCTGGAGAAGAGCCCTG GGAAACTTGTTGTCAAGATGCCTTTCCAAGCATC GCCTGGGGGTAAGGGTGAGGGAGGTGGGGCTA CCACATCTGCCCAGGTCATGGTGATCAAACGCCC TGGCAGAAAGCGAAAAGCTGAAGCTGACCCCCA GGCCATTCCTAAGAAACGGGGTAGAAAGCCTGG GAGTGTGGTGGCAGCTGCTGCAGCTGAGGCCA-3′	ThermoFisher Scientific (GeneArt Strings)	N/A
pEGFP-N1_MeCP2(WT)	Tillotson et al., 2017	RRID: Addgene_110186
pEGFP-N1_MeCP2(R111G)	Tillotson et al., 2017	RRID: Addgene_110187
pEGFP-N1_MeCP2(R306C)	Tillotson et al., 2017	RRID: Addgene_110188
pEGFP-N1_MeCP2(MM2)	This manuscript	N/A
pEGFP-N1_MeCP2(MM2-RG)	This manuscript	N/A
pmCherry-N1–TBL1X	Lyst et al., 2013	N/A
pET30b_MeCP2[N-term]	This manuscript	N/A
pET30b_MM2[N-term]	This manuscript	N/A
pX330-U6-Chimeric_BB-CBh-hSpCas9 with gRNA (GGTTGTGACCCGCCATGGAT)	Tillotson et al., 2017	N/A
Software and algorithms
Jalview 2.8.2	Barton lab, University of Dundee	www.jalview.org
FRAP Macro	This paper	GitHub: https://doi.org/10.5281/Zenodo.2654602
FACSDIVA version 8.0.1	BD Biosciences	N/A
ANYMaze	Stoelting	N/A
Prism 8	GraphPad	N/A
LAS AF software	Leica	N/A
Zen Black	Zeiss	N/A
Fiji	ImageJ	N/A
Image Studio Lite Ver 5.2	LI-COR	N/A
LightCycler 480 SW 1.5	Roche	N/A