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. 2017 Aug 30;7:9932. doi: 10.1038/s41598-017-09494-6

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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The deleterious effects mediated via the repression of activator E2Fs can be reversed within a limited time frame. (a) Histogram of total numbers of erythrocytes, leukocytes, and platelets in in E2f1 ^−/−; E2f2 ^−/−; E2f3 ^TRE/TRE control (n = 8) and E2f1 ^−/−; E2f2 ^−/−; E2f3 ^TRE/TRE; β-actin-tTS mice following withdrawal of 100 mg/L tetracycline for 2 weeks (−2, n = 3), or following removal of tetracycline for 2 weeks followed by re-administration of tetracycline for the indicated number of weeks (−2/+1, n = 3(erythrocytes), n = 2(leukocytes, platelets)) and (−2/+2, n = 5(erythrocytes, platelets), n = 4(leukocytes)), respectively. Error bars, s.e.m. Two-tailed t-test; -2weeks vs. −2/+2weeks, **P = 0.001(leukocytes), 0.04*(platelets). (b) Quantification of differentiated intestinal cells per villus or crypt (stained as in Fig. 5D) in E2f1 ^−/−; E2f2 ^−/−; E2f3 ^TRE/TRE control (n = 10(enteroendocrine, goblet), n = 9(Paneth)) and E2f1 ^−/−; E2f2 ^−/−; E2f3 ^TRE/TRE; β-actin-tTS mice following tetracycline removal for 2 weeks (-2, n = 2(enteroendocrine), n = 3 (goblet, Paneth)), or following removal of tetracycline for 2 weeks followed by re-administration of tetracycline for the indicated number of weeks (−2/+1, n = 2), (−2/+2, n = 5). Two-tailed t-test; -2weeks vs. −2/+2weeks, *P = 0.04 (goblet), 0.02*(Paneth).