Bromodomain protein Brd3 promotes Ifnb1 transcription via enhancing IRF3/p300 complex formation and recruitment to Ifnb1 promoter in macrophages
Authors: Kai Zhao
Qinlan Wang
Donghao Sun
Xingguang Liu
Dezhi Zhao
Xia Li
Qian Zhang
Nan Li
Chaofeng Han
Wenhui Ren
Chunmei Wang
Xuetao Cao
Jin Hou
Journal: Scientific reports (2017)
Discipline: Multidisciplinary
Keywords: bromodomain-containing proteins; Brd3; innate immune response; virus infection; IFN-β production
Affiliations: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China., Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China., Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China.

Abstract:  As members of bromodomain and extra-terminal motif protein family, bromodomain-containing proteins regulate a wide range of biological processes including protein scaffolding, mitosis, cell cycle progression and transcriptional regulation. The function of these bromodomain proteins (Brds) in innate immune response has been reported but the role of Brd3 remains unclear. Here we find that virus infection significantly downregulate Brd3 expression in macrophages and Brd3 knockout inhibits virus-triggered IFN-β production. Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection. Importantly, Brd3 promotes the recruitment of IRF3/p300 complex to the promoter of Ifnb1, and increases the acetylation of histone3/histone4 within the Ifnb1 promoter, leading to the enhancement of type I interferon production. Therefore, our work indicated that Brd3 may act as a coactivator in IRF3/p300 transcriptional activation of Ifnb1 and provided new epigenetic mechanistic insight into the efficient activation of the innate immune response. 

Retracted: No

PubPeer comments:
null, 
null, 
 Via https: www.ilfattoquotidiano.it in-edicola articoli 2019 11 28 ricerche-mediche-aggiustate-pero-la-scienza-tace 5583974 (and Google translate) Fixed medical research, but science is silent by Gianni Barbacetto | NOVEMBER 28, 2019 u201cFor justice everything is fine. But is this okay for the scientific community ? Is it possible to falsify the images of the experiments, or avoid doing the control experiment, without anyone having anything to say? These are the questions that remain, at the end of a long judicial investigation by the Milan Public Prosecutor s Office on some articles of the most important Italian scientists engaged in cancer research. Professor Alberto Mantovani of Humanitas, Pier Giuseppe Pelicci of Ieo, Pier Paolo Di Fiore of Ifom, Marco Pierotti, with Maria Angela Greco, Elena Tamburini and Silvana Pilotti of the Cancer Institute, were investigated by prosecutors Francesco Cajani and Paolo Filippini for having manipulated the images of some of their studies published in international scientific journals. They are research luminaries who maneuver millions of euros from public funds, private donations, 5 per thousand collections . They received, only in the period analyzed by the Public Prosecutor (2005-2012), very high figures: 9.37 million Di Fiore; 3.06 Mantovani; 1.48 Pelicci; 3.60 Pierotti, for a total of 17 million paid by the CNR , the Ministry of Health and the University. And they got caught  fixing their research records. Now the judge of the preliminary investigation Sofia Fioretta has closed the investigation started in 2014, dismissing the accusations and arguing - with bold arguments - that the professors  did not carry out any falsification activities  . The two prosecutors had already requested the filing, arguing that the manipulations are established, but that the crime of  scientific fraud does not exist in Italy (as there is instead that of insurance fraud and sports fraud), therefore it is not possible pursue the behaviors of the seven excellent oncologists. The investigating judge was more creative : he recognized  a harmless and innocent fake , realized  because there was no time or money to perform the replication, or because competitors were coming first (what stupid scientists who do everything right instead ). Therefore,  insignificant errors were made . Replicas of the experiments were not carried out, but this  did not affect the content of the research and  did not undermine the scientific validity of the published thesis . In short: the luminaries were wrong, but in modest quantity . Yet the examinations of the experts of the Public Prosecutor s Office have ascertained the manipulations: three in the works of Pelicci-Ieo, four in those of the group of Pierotti-Istituto dei tumori (i.e. two by Pilotti and one by Greco and Tamburini), one in the works by Di Fiore-Ifom and one by Mantovani-Humanitas. But nothing wrong with that, that s okay, the investigating judge Fioretta reassures us. Closed the judicial game, at this point we ask some questions to the scientific community: 1. Are there, in scientific practice,  harmless and innocent false manipulations , but  of little significance ? 2. Is it normal that seven luminaries of oncology research publish images in international scientific journals that are manipulated in 21 out of 27 cases analyzed? 3. Is it compatible with the scientific method that, having performed the first experiment, one tarot the replica,  because there was no time or money to perform it,  or because competitors were arriving first ? 4. Since it is impossible, on the judicial level, to establish the direct connection between research carried out and funds obtained, is it still normal, on the scientific and ethical level, to obtain money, public and private, with the prestige gained (also) with fake research? 5. Is the scientific community sure that squaring up (corporately) and rejoicing in the  false innocents is the best way to defend science and the scientific method, now threatened by charlatans, scoundrels and no-vaxes?u201d ,