The TRRAP transcription cofactor represses interferon-stimulated genes in colorectal cancer cells.
PIKK
chaperone
chromosomes
colorectal cancer
gene expression
human
interferon
transcription
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
04 03 2022
04 03 2022
Historique:
received:
23
04
2021
accepted:
03
03
2022
pubmed:
5
3
2022
medline:
30
4
2022
entrez:
4
3
2022
Statut:
epublish
Résumé
Transcription is essential for cells to respond to signaling cues and involves factors with multiple distinct activities. One such factor, TRRAP, functions as part of two large complexes, SAGA and TIP60, which have crucial roles during transcription activation. Structurally, TRRAP belongs to the phosphoinositide 3 kinase-related kinases (PIKK) family but is the only member classified as a pseudokinase. Recent studies established that a dedicated HSP90 co-chaperone, the triple T (TTT) complex, is essential for PIKK stabilization and activity. Here, using endogenous auxin-inducible degron alleles, we show that the TTT subunit TELO2 promotes TRRAP assembly into SAGA and TIP60 in human colorectal cancer cells (CRCs). Transcriptomic analysis revealed that TELO2 contributes to TRRAP regulatory roles in CRC cells, most notably of MYC target genes. Surprisingly, TELO2 and TRRAP depletion also induced the expression of type I interferon genes. Using a combination of nascent RNA, antibody-targeted chromatin profiling (CUT&RUN), ChIP, and kinetic analyses, we propose a model by which TRRAP directly represses the transcription of
Identifiants
pubmed: 35244540
doi: 10.7554/eLife.69705
pii: 69705
pmc: PMC8926402
doi:
pii:
Substances chimiques
Transcription Factors
0
Interferons
9008-11-1
Histone Acetyltransferases
EC 2.3.1.48
Banques de données
GEO
['GSE171454', 'GSE192527', 'GSE50954', 'GSM945853', 'GSM945304']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Detilleux et al.
Déclaration de conflit d'intérêts
DD, PR, BP, DH No competing interests declared
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