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. Author manuscript; available in PMC: 2023 May 1.
Published in final edited form as: Trends Biochem Sci. 2022 May;47(5):417–432. doi: 10.1016/j.tibs.2022.03.002

Table 1.

Reader-effector proteinsa, their functional domains, biological activity, and misregulation in human diseaseb

RE (Uniprot) Chromatin signal(s) Reader domain(s) Effector domain(s) Interacting effector(s) Misregulation in human disease
Positive regulation of transcription and/ or elongation
BRD4 (O60885) H3/H4Kac BRD

  1. ET domain

  2. CK2-phosphorylated region

  3. CTM

  1. NSD3, JMJD6, CHD4, GLTSCR1, ATAD5

  2. TP53

  3. P-TEFb complex (CDK9, CCNT1)

 Cancer: fusion [81,82]
BRD4S, short isoform H3/H4Kac BRD

  1. ET domain

  2. CK2-phosphorylated region

  1. NSD3, JMJD6, CHD4, GLTSCR1, ATAD5

  2. TP53

 Cancer: overexpressed [83]
PcTF H3K27me3 CD VP64 MED15, MED17, TFII, TBP [84] Not applicable
TRIM24 (O15164)

  1. H3K4me0

  2. H3K23ac

  1. PHD

  2. BRD

 RBCC E3 ubiquitin ligase domain Coactivators (e.g., NCOA2, CARM1), corepressors (e.g., CBX1/3/5) Cancer: overexpressed [85]
AF9 (P42568) H3K9cr, H3K9ac, H3K9bu YEATS Disordered C-terminal region SEC (EAF1, EAF2, CDK9, AFF), P-TEFb complex, ELL Cancer: fusion [86]
ENL (Q03111) H3K9ac, H3K9cr YEATS Disordered C-terminal region SEC (AFF4, CDK9), ALKBH4, EBAFb complex Cancer: fusion [86], mutated [87], overexpressed [19,20]
Negative regulation of transcription
BAHCC (Q9P281) H3K27me3
H3K4me3		 BAH
PHD		 Disordered N-terminal region SAP30BP, HDAC1, ING Cancer: overexpressed [24]
EBSc (F4JL28)

  1. H3K27me3

  2. H3K4me3

  1. BAH

  2. PHD

 Undetermined MSI4, HDACs Not applicable
SHLc (Q9FEN9)

  1. H3K27me3

  2. H3K4me3

  1. BAH

  2. PHD

 Disordered C-terminal region MSI4, HDACs Not applicable
CBX1/HP1a (P83916) H3K9me3 CD Disordered region, chromoshadow domain HMTs (SUV39H1, SETDB1, KMT5B, KMT5C) Cancer: overexpressed [88]
CBX2 (Q14781) H3K27me3 CD Polycomb box Polycomb repressive complex 1: RING1A/B, BMI1, PHC Cancer: overexpressed [43,44]
HP1ad (P05205) H3K9me3 CD Chromoshadow domain
MeCP2 (P51608) 5meCpG MBD NID Nuclear receptor corepressor 2 Neurological: mutated [47–50], underexpressed [51]
MBD1 (Q9UIS9) 5meCpG MBD TRD Cancer: overexpressed [89]
MBD2 (Q9UBB5) 5meCpG MBD TRD Nucleosome remodeling and deacetylase (Mi-2/NuRD) complex, Sin3A Cancer: overexpressed [90–92]
Immune: overexpressed [56,58], underexpressed [57]
MBD4 (O95243) 5meCpG MBD TRD Sin3A, HDAC1, DNMT1, DNMT3B Cancer: overexpressed [92]
Immune: overexpressed [56,58], underexpressed [57]
Neurological: mutated [93,94], overexpressed [58,95], underexpressed [57]
Chromatin remodeling
BPTF (Q12830)

  1. H3K9ac, H3K14ac

  2. H3K4me3/2

  1. BRD

  2. PHD

 Coiled-coil and disordered regions Nucleosome remodeling factor complex Cancer: overexpression [45]
Neurological: mutated [96]
p300 (Q09472)

  1. H3Kac

  2. H3A1-T22

  1. BRD

  2. ZZ

 Acetyltransferase targeting histones and non-histone proteins Cancer: fusion [97]
AIRE (O43918) H3K4 PHD Caspase recruitment domain, SAND domain Immune: mutated [54,55]
RAG2 (P55895) H3K4me3 PHD Disordered central region RAG complex (RAG1, HMGB1/2) Immune: mutated [52]
YEATS2 (Q9ULM3) H3K27ac, H3K27cr YEATS Disordered N- and C-terminal regions GCN5, PCAF Cancer: overexpressed [21]
ZZZ3 (Q8IYH5) H3A1-A21 ZZ Disordered N-terminal region CRBP2; ATAC (KAT14, KAT2A, TADA2L, TADA3L, MBIP, WDR5, YEATS2, CCDC101, DR1) Not applicable
a

The table includes RE proteins mentioned in this review and select additional REs that are associated with human diseases. REs are grouped by their biological outputs and by reader domain type. The corresponding chromatin signals, reader domains, effector domains, and other effector proteins that interact with the RE are described in the literature cited by the Uniprot database entry for each RE, and by work cited in this review.

b

Abbreviations: ALKBH4, AlkB homolog 4, lysine demethylase; ATAC, ADA2A-containing complex; ATAD5, ATPase family AAA domain containing 5; BMI1, polycomb complex protein BMI-1; CARM1, coactivator associated arginine methyltransferase 1; CHD4, chromodomain-helicase-DNA-binding protein 4; CRBP2, cellular retinol binding protein 2; CTM, C-terminal motif; DNMT1, DNA methyltransferase 1; DNMT3B, DNA methyltransferase 3 beta; ELL, elongation factor for RNA polymerase II; ET, extraterminal; GLTSCR1, glioma tumor suppressor candidate region gene 1; HDAC, histone deacetylase; HMGB1/2, high mobility group box 1 protein 1/2; HMT, histone methyltransferase; JMJD6, Jumonji domain containing 6; KMT5B, lysine methyltransferase 5B; KMT5C, lysine methyltransferase 5C; MED15, mediator complex subunit 15; MED17, mediator complex subunit 17; MSI4, WD-40 repeat-containing protein MSI4; NCOA2, nuclear receptor coactivator 2; NID, NCoR/SMRT interaction domain; n/a, not available; NSD3, nuclear receptor binding SET domain protein 3; P-TEFb, positive transcription elongation factor b; RAG, recombination activating gene; RBCC, ring, B-Box and coiled-coil; RING1A/B, ring finger protein 1A/B; SAND, human Sp100, Aire1, NucP41/P75, and Drosophila DEARF1; SEC, super elongation complex; SETDB1, SET domain bifurcated histone lysine methyltransferase 1; SIN3A, SIN3 transcription regulator family member A; SUV39H1, SUV39H1 histone lysine methyltransferase); TBP, TATA-binding protein; TP53, tumor protein 53; TRD, transcription repression domain.

c

Arabidopsis thaliana (plant).

d

Drosophila melanogaster (fly).