Evidence map›Paper›PMID 35904816›Full record

ArticleNucleic acids research2022

FACT subunit SUPT16H associates with BRD4 and contributes to silencing of interferon signaling.

Dawei Zhou, Zhenyu Wu, Jun-Gyu Park, Guillaume N Fiches, Tai-Wei Li, Qin Ma, Huachao Huang, Ayan Biswas, Luis Martinez-Sobrido, Netty G Santoso and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 18 citations in OpenAlex.

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  11. Altered histone modifications inbioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Dawei ZhouDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Zhenyu WuDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Jun-Gyu ParkTexas Biomedical Research Institute, San Antonio, TX 78227, USA.
Guillaume N FichesDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Tai-Wei LiDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0002-7364-0805
Qin MaDepartment of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Huachao HuangDepartment of Medicine, Columbia University Medical Center, NY, NY 10032, USA.
Ayan BiswasDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Luis Martinez-SobridoTexas Biomedical Research Institute, San Antonio, TX 78227, USA.
Netty G SantosoDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0003-1175-5831
Jian ZhuDepartment of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.ORCID 0000-0001-9856-8320
The Ohio State University Wexner Medical Center · USTexas Biomedical Research Institute · USColumbia University Irving Medical Center · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Daniel G. Stover · 1985 to 2026
$132.3M
Investigation of Latency Promoting Genes (LPGs) in HIV Oral Reservoir CellsR01DE025447 · NIDCR · UNIVERSITY OF ROCHESTER · PI ZHU, JIAN · 2015 to 2019
$1.9M
(PQ4) Role of HIV-induced PLK1 Activation in Regulation of gamma-Herpesvirus Reservoirs in LymphocytesR01CA260690 · NCI · OHIO STATE UNIVERSITY · PI SANTOSO, NETTY G · 2021 to 2025
$1.9M
Cooperation of BRD4 and TAT Associated Proteins in HIV Transcription and LatencyR33AI116180 · NIAID · UNIVERSITY OF ROCHESTER · PI ZHU, JIAN · 2016 to 2018
$1.2M
Role of RNA Methylation in Regulating HIV Proviral ExpressionR56AI157872 · NIAID · OHIO STATE UNIVERSITY · PI ZHU, JIAN · 2021 to 2021
$374k
Inhibition of TIP60 by Latent Gammaherpesviruses in B-cell LymphomasR03DE029716 · NIDCR · OHIO STATE UNIVERSITY · PI SANTOSO, NETTY G · 2020 to 2021
$312k
Role of FACT Proteins in Regulating HIV Transcription and LatencyR01AI150448 · NIAID · OHIO STATE UNIVERSITY · PI ZHU, JIAN · 2019 to 2019
$300k
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA260690NIAID NIH HHS R01 AI150448NIAID NIH HHS R33 AI116180NIAID NIH HHS R56 AI157872NIDCR NIH HHS R01 DE025447NIDCR NIH HHS R03 DE029716
6 · The paper itself

Abstract

FACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated in both epithelial and natural killer (NK) cells. The histone acetyltransferase TIP60 contributes to the acetylation of SUPT16H middle domain (MD) at lysine 674 (K674). Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H in both epithelial and NK cells. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (HDAC1, EZH2), and further regulates their activation status and/or promoter association as well as affects the relevant histone marks (H3ac, H3K9me3 and H3K27me3). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, depletion or inhibition of SUPT16H is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that depletion or inhibition of SUPT16H also causes the remarkable activation of IFN signaling in NK cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in coordinating with BRD4 and regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of the FACT inhibitor CBL0137 to treat viral infections.

Indexed as

Signal TransductionBromodomain Containing ProteinsCell Cycle ProteinsCOVID-19DNA-Binding ProteinsEpithelial CellsHigh Mobility Group ProteinsHumansInterferonsKiller Cells, NaturalNuclear ProteinsSARS-CoV-2Transcriptional Elongation FactorsTranscription FactorsZika VirusZika Virus InfectionBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsDNA-Binding ProteinsHigh Mobility Group ProteinsInterferonsNuclear ProteinsSSRP1 protein, humanSUPT16H protein, humanTranscriptional Elongation FactorsTranscription Factors

Identifiers

PMID35904816
PMCPMC9410884
OpenAlexW4288715917

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.