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dc.contributor.authorKong, IY
dc.contributor.authorRimes, JS
dc.contributor.authorLight, A
dc.contributor.authorTodorovski, I
dc.contributor.authorJones, S
dc.contributor.authorMorand, E
dc.contributor.authorKnight, DA
dc.contributor.authorBergman, YE
dc.contributor.authorHogg, SJ
dc.contributor.authorFalk, H
dc.contributor.authorMonahan, BJ
dc.contributor.authorStupple, PA
dc.contributor.authorStreet, IP
dc.contributor.authorHeinzel, S
dc.contributor.authorBouillet, P
dc.contributor.authorJohnstone, RW
dc.contributor.authorHodgkin, PD
dc.contributor.authorVervoort, SJ
dc.contributor.authorHawkins, ED
dc.date.accessioned2020-11-27T00:53:43Z
dc.date.available2020-11-27T00:53:43Z
dc.date.issued2020-10-20
dc.identifierpii: S2211-1247(20)31279-1
dc.identifier.citationKong, I. Y., Rimes, J. S., Light, A., Todorovski, I., Jones, S., Morand, E., Knight, D. A., Bergman, Y. E., Hogg, S. J., Falk, H., Monahan, B. J., Stupple, P. A., Street, I. P., Heinzel, S., Bouillet, P., Johnstone, R. W., Hodgkin, P. D., Vervoort, S. J. & Hawkins, E. D. (2020). Temporal Analysis of Brd4 Displacement in the Control of B Cell Survival, Proliferation, and Differentiation. CELL REPORTS, 33 (3), https://doi.org/10.1016/j.celrep.2020.108290.
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/11343/252630
dc.description.abstractJQ1 is a BET-bromodomain inhibitor that has immunomodulatory effects. However, the precise molecular mechanism that JQ1 targets to elicit changes in antibody production is not understood. Our results show that JQ1 induces apoptosis, reduces cell proliferation, and as a consequence, inhibits antibody-secreting cell differentiation. ChIP-sequencing reveals a selective displacement of Brd4 in response to acute JQ1 treatment (<2 h), resulting in specific transcriptional repression. After 8 h, subsequent alterations in gene expression arise as a result of the global loss of Brd4 occupancy. We demonstrate that apoptosis induced by JQ1 is solely attributed to the pro-apoptotic protein Bim (Bcl2l11). Conversely, cell-cycle regulation by JQ1 is associated with multiple Myc-associated gene targets. Our results demonstrate that JQ1 drives temporal changes in Brd4 displacement that results in a specific transcriptional profile that directly affects B cell survival and proliferation to modulate the humoral immune response.
dc.languageEnglish
dc.publisherCELL PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleTemporal Analysis of Brd4 Displacement in the Control of B Cell Survival, Proliferation, and Differentiation
dc.typeJournal Article
dc.identifier.doi10.1016/j.celrep.2020.108290
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleCell Reports
melbourne.source.volume33
melbourne.source.issue3
dc.rights.licensecc-by-nc-nd
melbourne.elementsid1469206
melbourne.contributor.authorFalk, Hendrik
melbourne.contributor.authorHawkins, Edwin
melbourne.contributor.authorJohnstone, Ricky
melbourne.contributor.authorMonahan, Brendon
melbourne.contributor.authorHeinzel, Susanne
melbourne.contributor.authorVervoort, Stephanus
melbourne.contributor.authorHogg, Simon
melbourne.contributor.authorBouillet, Philippe
melbourne.contributor.authorStreet, Ian
melbourne.contributor.authorHodgkin, Philip
melbourne.contributor.authorLight, Amanda
melbourne.contributor.authorTodorovski, Izabela
dc.identifier.eissn2211-1247
melbourne.accessrightsOpen Access


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