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. 2023 Sep 7;24(18):13807. doi: 10.3390/ijms241813807

Table 1.

Chromatin and transcription factors directly or indirectly regulated by TDP-43 and modifying TDP-43-induced toxicity.

Gene Symbol Name Mammalian Orthologs *, Alias Gene Ontology Function Contribution to Chromatin
Structure/Transcription
Toxicity Modulation
upon Knockdown
Refs.
Chd1  Chromodomain-helicase-DNA binding protein 1 CHD1, CHD2 Chromatin remodeling SILENCING suppresses/ameliorates [52]
e(y)3  Enhancer of yellow 3 PHF10 Chromatin remodeling OPENING suppresses/ameliorates [52]
polybromo  Polybromo BAF180 Chromatin remodeling OPENING suppresses/ameliorates [52]
ash1  Absent, small, or homeotic discs 1 ASH1L Chromatin remodeling OPENING suppresses/ameliorates [52]
enok  Enoki mushroom KAT6A Chromatin remodeling OPENING suppresses/ameliorates [52]
br  Broad - Chromatin remodeling OPENING suppresses/ameliorates [52]
Br140  Bromodomain-containing protein, 140kD BRPF1 Chromatin remodeling OPENING suppresses/ameliorates [52]
mor  Moira BAF170S/MARCC2 Chromatin remodeling OPENING suppresses/ameliorates [52]
MED8  Mediator complex subunit 8 MED8 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED11  Mediator complex subunit 11 MED11 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED15  Mediator complex subunit 15 MED15 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED21  Mediator complex subunit 21 MED21 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED22  Mediator complex subunit 22 MED22 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED27  Mediator complex subunit 27 MED27 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED28  Mediator complex subunit 28 MED28 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
MED31  Mediator complex subunit 31 MED31 Mediator complex TF–RNA Pol interaction suppresses/ameliorates [52]
e(y)1  Enhancer of yellow 1 TAF9 Transcription Factor Transcription suppresses/ameliorates [52]
TAF1  TBP-associated factor 1 TAF1 Transcription Factor Transcription suppresses/ameliorates [52]
Tomb  tombola LIN54/TESMIN ** Male meiosis Transcription suppresses/ameliorates [52]
Su(Tpl)  Suppressor of Triplolethal ELL, ELL2 Elongator Transcription suppresses/ameliorates [52]
SF2  Splicing factor 2 SRSF1 Splicing Transcription suppresses/ameliorates [52]
Hsp70B (Ba/Bb/Bbb/Bc)  Heat-shock-protein-70B (Ba/Bb/Bbb/Bc) HSPA1A Heat shock Factor Transcription suppresses/ameliorates [52]
Chd1  Chromodomain-helicase-DNA-binding protein 1 CHD1 Chromatin remodeling TDP-1/TDP-43 impedes Chd1 binding strongly enhances [51]
dom  Domino SRCAP ** Chromatin remodeling strongly enhances [51]
mi-2  Mi-2 CHD3; CHD4; CHD5 ** Chromatin remodeling enhances [51]
kis  Kismet CHD6, CHD7, CHD8, CHD9 ** Chromatin remodeling enhances [51]
asf1  Anti-silencing factor 1 ASF1A; ASF1B Chromatin remodeling suppresses [51]
Snr1  Snf5-related 1 SMARCB1 Chromatin remodeling suppresses [51]
mor  Moira SMARRC1; SMARCC2 ** Chromatin remodeling suppresses [51]
Dalao  Brahma associated protein 111kD, Bap111 SMARCE1 ** Chromatin remodeling suppresses [51]
Chd3  Chd3 CHD3 Chromatin remodeling suppresses [51]
Bap60  Brahma associated protein 60kD SMARCD1 Chromatin remodeling strongly suppresses [51]
MBD-R2  MBD-R2 PHF20; PHF20L1 Histone Lysine acetyltransferase OPENING enhances [51]
Tip60  Tat interactive protein 60kDa KAT5; KAT7; KAT8 ** Histone Lysine acetyltransferase OPENING enhances [51]
CG2051  Histone acetyltransferase 1 HAT1 Histone Lysine acetyltransferase OPENING suppresses [51]
HDAC3  Histone deacetylase 3 HDAC3 Histone Lysine deacetylase SILENCING enhances [51]
Mta1-like  Metastasis associated 1-like MTA2; MTA3 Histone Lysine deacetylase SILENCING enhances [51]
Sirt4  Sirtuin 4 SIRT4 Histone Lysine deacetylase SILENCING suppresses [51]
HDAC6  Histone deacetylase 6 HDAC6 Histone Lysine deacetylase SILENCING suppresses * [51]
Scm  Sex comb on midleg L3MBTL3; PHC2; SCML1; THAP10 Transcription Factor Transcription suppresses [51]
Spt6  Spt6 SUPT6H Transcription Factor Transcription suppresses [51]
lid  Little imaginal discs KDM 4A; 4B; 4D; 4E; 4F; 5A; 5B; 5C; 5D; Histone Lysine demethylase (H3K4) SILENCING strongly suppresses [51]
Utx  Utx histone demethylase KDM6A; 6B; UTY Histone Lysine demethylase (H3K27) OPENING suppresses [51]
Asx  Additional sex combs ASXL1-3 Chromatin regulator SILENCING suppresses [51]
Ncoa6  Nuclear receptor coactivator 6 NCOA6 co-activator Transcription suppresses [51]
Su(var)3-9  Suppressor of variegation 3-9 SUV39H1 Histone Lysine methyltransferase (H3K9) SILENCING suppresses [51]
ash2  Absent, small, or homeotic discs 2 ASH2L Histone Lysine methyltransferase (H3K4) OPENING enhances [51]
Su(z)2  Suppressor of zeste 2 BMI1; PCGF1; 2; 5; 6; RING1B; RNF2 Histone Lysine methyltransferase,
histone monoubiquitination (H2A-K119)
OPENING enhances [51]
Set1  SET domain containing 1 KMT2B Histone Lysine methyltransferase (H3K4) OPENING enhances [51]
Wdr82  WD repeat domain 82 WDR82 Histone Lysine methyltransferase (H3K4) OPENING enhances [51]
HPL-2 †2 Heterochromatin Protein-like 2 HPL1 Chromatin remodeling TDP-1 bridges HPL-2 to chromatin n.d. [53]
nBAF complex Neuronal Brg1/BRM Associated factor SS18L1, NBAF; CREST; SYT homolog 1 Neuronal chromatin remodeling complex nBAF component n.d. [57]
sgg  Shaggy GSK3 Control of cellular pathways and metabolism suppresses [50]
htk  Hat-trick Chromatin remodeling suppresses [50]
xmas-2  Xmas-2 Transcription and RNA export suppresses [50]
H3C14 H3S10Ph-K14Ac: Histone 3 (serine 10 phosphorylation/lysine 14 acetylation) H3 Histone tail PTM Transcriptional activation/repression n.d. [58]
H3C14 H3K9me3: Histone 3 (methylation of lysine 9) H3 Histone tail PTM Transcriptional repression n.d. [58]
HDAC1 Histone deacetylase 1 HDAC1 Histone/Protein Lysine deacetylase SILENCING *** n.d. [48]
H2b Histone cluster 1, H2bp HIST1H2BP Nucleosome assembly Downregulated in the TDPΔNLS n.d. [63]
H3d Histone cluster 1, H3d HIST1H3D Nucleosome assembly Downregulated in the TDPΔNLS n.d. [63]
H4a/H4b/H4c/H4h Histone cluster 1, H4a, b, c, h HIST1H4 Nucleosome assembly Downregulated in the TDPΔNLS n.d. [63]
Nap1l1 Nucleosome assembly protein 1-like1 NAP1L1 Nucleosome assembly Upregulated in the TDPΔNLS n.d. [63]
Med20 Mediator Complex subunit 20 MED20; SRB2; TRFP; PRO0213 Mediator Complex/transcriptional coactivator Transcriptional activation n.d. [64]
Usp49 Ubiquitin specific processing protease 49 USP49 H2B Histone deubiquitinase Transcriptional activation/regulation of mRNA splicing n.d. [64]
HUWE1 HECT, UBA, WWE domain Containing E3 Ubiquitin Protein ligase 1 HUWE1 Histone/protein Ubiquitination n.d. [65]
YY1 Yin and Yang 1 transcription Factor YY-1; INO80S Transcription factor Transcriptional activation/repression n.d. [65]
MORF4L2 Mortality Factor 4-like 2 MRGX; KIAA0026; MORF-Related Gene X Heterochromatin assembly/histone modification Transcriptional activation n.d. [65]
HMGN1 High-Mobility Group Nucleosome Binding Domain 1 HMG14; MGC104230; FLJ27265 Chromatin remodeling n.d. [65]
PRKDC Protein Kinase, DNA-Activated, Catalytic subunit DNA-PKcs; DNPK1; P460; DNAPKc; XRCC7; P350 DNA repair and recombination n.d. [65]
UIMC1 Ubiquitin Interaction Motif Containing 1 RAP80; Retinoid X Receptor-Interacting Protein 110 DNA repair Ubiquitination/Transcription repression n.d. [65]
POLB DNA Pol Beta DNA Pol Beta DNA excision and repair n.d. [65]
SFPQ Splicing Factor Proline and Glutamine Rich PSF; PPP1R140; HPOMp100; POMP100 Splicing Enables DNA binding activity n.d. [65]
MSH3 MutS Homolog 3 MRP1; DUP; HMSH3; Mismatch Repair Protein DNA mismatch repair system (MMR) Postreplicative DNA mismatch repair n.d. [65]
XRCC5 X-Ray Repair Cross Complementing 5 Ku86; KARP-1; KU80; KUB2 DNA repair DNA DSB repair by NHEJ n.d. [65]
XRCC6 X-RAY Repair Cross Complementing 6 KU70; Cells6; G22P1; ML8 DNA repair DNA DSB repair by NHEJ n.d. [65]
STAG2 Stromal Antigen 2 SA2; SCC3B; SA-2; Cohesin Subunit SA-2 Chromatin remodeling Cohesion of sister chromatids after DNA replication n.d. [77,78]
Ell, Su(Tpl)  Elongation Factor for RNA Pol II ELL; ELL2; C19orf17; PPP1R68 Elongator Transcription regulation enhances [52,79]

Flybase, †2 Wormbase * Mammalian Orthologs from referenced work or from OrthoDB database. ** Contribution to chromatin structure/transcription. Source: referenced work, OrthoDB, NCBI, or UniProt databases. *** Potentially by acting directly on TDP-43 acetylation. Histone PTM stands for histone post-transcriptional modification.