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Interferon\u2010<jats:italic>\u03b3<\/jats:italic>is secreted at the fetal\u2013maternal interface in pregnant women and mice. The outer layer of the placenta in contact with maternal blood is composed of semi\u2010allogeneic trophoblast cells, which constitute the fetal component of the fetal\u2013maternal interface. The simultaneous presence of pro\u2010inflammatory<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic>and trophoblast cells at the fetal\u2013maternal interface appears to represent an immunological paradox, for trophoblastic responses to<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic>could potentially lead to activation of maternal immunity and subsequent attack of the placenta. However, our previous studies demonstrate that<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic>responsive gene (<jats:styled-content style=\"fixed-case\">IRG<\/jats:styled-content>) expression is negatively regulated in human and mouse trophoblast cells. In human cytotrophoblast and trophoblast\u2010derived choriocarcinoma cells, janus kinase signalling is blocked by protein tyrosine phosphatases (<jats:styled-content style=\"fixed-case\">PTP<\/jats:styled-content>s), whereas in mouse trophoblast, histone deacetylases (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s) inhibit<jats:styled-content style=\"fixed-case\">IRG<\/jats:styled-content>expression. Here, we used genome\u2010wide transcriptional profiling to investigate the collective roles of<jats:styled-content style=\"fixed-case\">PTP<\/jats:styled-content>s and<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s on regulation of<jats:styled-content style=\"fixed-case\">IRG<\/jats:styled-content>expression in human choriocarcinoma cells. Logic\u2010rules were optimized to derive regulatory modes governing gene expression patterns observed upon different combinations of treatment with<jats:styled-content style=\"fixed-case\">PTP<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>inhibitors. The results demonstrate that<jats:styled-content style=\"fixed-case\">IRG<\/jats:styled-content>s can be divided into several categories in human choriocarcinoma cells, each of which is subject to distinct mechanisms of repression. Hence, the regulatory modes identified in this study suggest that human trophoblast and choriocarcinoma cells may evade the potentially deleterious consequences of exposure to<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic>by using several overlapping mechanisms to block<jats:styled-content style=\"fixed-case\">IRG<\/jats:styled-content>expression.<\/jats:p>","DOI":"10.1111\/imm.12707","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T07:22:43Z","timestamp":1483600963000},"page":"71-80","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Optimized logic rules reveal interferon\u2010<i>\u03b3<\/i>\u2010induced modes regulated by histone deacetylases and protein tyrosine phosphatases"],"prefix":"10.1111","volume":"151","author":[{"given":"Daniel","family":"Van Twisk","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Rochester Rochester NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Rochester Rochester NY USA"},{"name":"Department of Obstetrics and Gynecology University of Rochester Rochester NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4479-4183","authenticated-orcid":false,"given":"Juilee","family":"Thakar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Rochester Rochester NY USA"},{"name":"Biostatistics and Computational Biology University of Rochester Rochester NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2422"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1226"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod61.2.493"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod46.6.1176"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.4049\/jimmunol.160.2.545","article-title":"Cytokine\u2010dependent abortion in CBA \u00d7 DBA\/2 mice is mediated by the procoagulant fgl2 prothrombinase [correction of prothombinase]","volume":"160","author":"Clark DA","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2004.00237.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2013.06.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60659-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.01.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1897"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.3.1598"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802454"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp1137"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1196"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-98141-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt997"},{"key":"e_1_2_8_23_1","unstructured":"ShannonP.MotifDb: An Annotated Collection of Protein\u2010DNA. 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