{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:35:42Z","timestamp":1784010942379,"version":"3.55.0"},"reference-count":82,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"The National Science Centre","doi-asserted-by":"publisher","award":["2018\/31\/B\/NZ4\/01379"],"award-info":[{"award-number":["2018\/31\/B\/NZ4\/01379"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The correct phagocytic activity of microglia is a prerequisite for maintaining homeostasis in the brain. In the analysis of mechanisms regulating microglial phagocytosis, we focused on the bromodomain and extraterminal domain (BET) proteins: Brd2, Brd3, and Brd4, the acetylation code readers that control gene expression in cooperation with transcription factors. We used pharmacological (JQ1) and genetic (siRNA) inhibition of BET proteins in murine microglial cell line BV2. Inhibition of BET proteins reduced the phagocytic activity of BV2, as determined by using a fluorescent microspheres-based assay and fluorescently labelled amyloid-beta peptides. Gene silencing experiments demonstrated that all brain-existing BET isoforms control phagocytosis in microglia. From a set of 84 phagocytosis-related genes, we have found the attenuation of the expression of 14: Siglec1, Sirpb1a, Cd36, Clec7a, Itgam, Tlr3, Fcgr1, Cd14, Marco, Pld1, Fcgr2b, Anxa1, Tnf, Nod1, upon BET inhibition. Further analysis of the mRNA level of other phagocytosis-related genes which were involved in the pathomechanism of Alzheimer\u2019s disease demonstrated that JQ1 significantly reduced the expression of Cd33, Trem2, and Zyx. Our results indicate the important role of BET proteins in controlling microglial phagocytosis; therefore, targeting BET may be the efficient method of modulating microglial activity.<\/jats:p>","DOI":"10.3390\/ijms24010013","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T04:45:53Z","timestamp":1671511553000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Bromodomain and Extraterminal (BET) Proteins in Controlling the Phagocytic Activity of Microglia In Vitro: Relevance to Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Marta","family":"Matuszewska","sequence":"first","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, ul. Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-4371","authenticated-orcid":false,"given":"Magdalena","family":"Cie\u015blik","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, ul. Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-5168","authenticated-orcid":false,"given":"Anna","family":"Wilkaniec","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, ul. Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-0878","authenticated-orcid":false,"given":"Marcin","family":"Strawski","sequence":"additional","affiliation":[{"name":"Laboratory of Electrochemistry, Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7541-1571","authenticated-orcid":false,"given":"Grzegorz A.","family":"Czapski","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, ul. Pawi\u0144skiego 5, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev-immunol-032713-120240","article-title":"Microglia development and function","volume":"32","author":"Nayak","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1111\/febs.14323","article-title":"Neurophagy, the phagocytosis of live neurons and synapses by glia, contributes to brain development and disease","volume":"285","author":"Vilalta","year":"2018","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tremblay, M., Lowery, R.L., and Majewska, A.K. (2010). Microglial interactions with synapses are modulated by visual experience. 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