Abstract
Abstract Reader proteins of histone modifications are required to translate the information of histone marks into the cellular phenotypes, including pluripotency and malignancy. For example, a reader protein BRD4 has its target specificity and becomes a target of cancer therapy. Here, we aimed to identify reader proteins involved in the pluripotency of stem cells. Using the UCSC database, 11 genes coding chromo- or PHD-domain proteins were isolated as actively transcribed in mouse ES cells (ESCs). Among the 11 genes, Cdyl2, chromodomain protein Y-like2, was found to be down-regulated upon ESC differentiation using RT-qPCR. Immunofluorescence and ChIP assay revealed that Cdyl2 recognized H3K27me3 of the specific regions, including differentiation-associated genes. Cdyl2-knock-out ESCs could not survive after differentiation induced by LIF removal or retinoic acid because of the induction of apoptosis, indicating that Cdyl2 is important for normal differentiation of ESCs. ESC expressing exogenous Cdyl2 showed incomplete down-regulation of Oct-4 and Nanog by retinoic acid, and generated teratomas with an abnormal composition of three germ layers, showing perturbation of differentiation ability. Pathologically, aberrant expression of human CDYL2 was observed in breast cancer cell lines and primary breast cancers. Two breast cancer cell lines (MDA-MB-231 and MDA-MB-468) expressing exogenous CDYL2 showed enhanced attachment ability along with the up-regulation of integrin alpha-6 and integrin beta-1. The population of cancer stem cells, defined as ALDH positive cells, were increased in CDYL2-expressing MDA-MB-468 cells, showing that human CDYL2 is involved in proliferation of cancer stem cells. From these data, we conclude that, between self-renewal and differentiation of stem cells, mouse and human Cdyl2/CDYL2 is necessary for the implementation of the initial step of differentiation. Citation Format: Naoko Hattori, Kana Kimura, Jumpei Taguchi, Toshio Imai, Yasuhiro Yamada, Toshikazu Ushijima. Cdyl2 is a chromodomain protein involved in the maintenance of pluripotency of stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 921. doi:10.1158/1538-7445.AM2017-921
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