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Background   Yin Yang 2  (YY2) is a zinc finger protein closely related to the well-characterized  Yin Yang 1  (YY1). YY1 is a DNA-binding transcription factor, with defined functions in multiple developmental processes, such as implantation, cell differentiation, X inactivation, imprinting and organogenesis.  Yy2  has been treated as a largely immaterial duplication of  Yy1 , as they share high homology in the Zinc Finger-region and similar if not identical  in vitro  binding sites. In contrast to these similarities, gene expression alterations in HeLa cells with attenuated levels of either  Yy1  or  Yy2  were to some extent gene-specific. Moreover, the chromatin binding sites for YY2, except for its association with transposable retroviral elements (RE) and Endogenous Retroviral Elements (ERVs), remain to be identified. As a first step towards defining potential  Yy2  functions matching or complementary to  Yy1 , we considered  in vivo  DNA binding sites of YY2 in trophoblast stem (TS) cells.    Results  We report the presence of YY2 protein in mouse-derived embryonic stem (ES) and TS cell lines. Following up on our previous report on ERV binding by YY2 in TS cells, we investigated the tissue-specificity of REX1 and YY2 binding and confirm binding to RE/ERV targets in both ES cells and TS cells. Because of the higher levels of expression, we chose TS cells to understand the role of  Yy2  in gene and chromatin regulation. We used  in vivo  YY2 association as a measure to identify potential target genes. Sequencing of chromatin obtained in chromatin-immunoprecipitation (ChIP) assays carried out with αYY2 serum allowed us to identify a limited number of chromatin targets for YY2. Some putative binding sites were validated in regular ChIP assays and gene expression of genes nearby was altered in the absence of  Yy2 .    Conclusions  YY2 binding to ERVs is not confined to TS cells.  In vivo  binding sites share the presence of a consensus binding motif. Selected sites were uniquely bound by YY2 as opposed to YY1, suggesting that YY2 exerts unique contributions to gene regulation. YY2 binding was not generally associated with gene promoters. However, several YY2 binding sites are linked to long noncoding RNA ( lncRNA ) genes and we show that the expression levels of a few of those are  Yy2 -dependent.

In Vivo Chromatin Targets of the Transcription Factor Yin Yang 2 in Trophoblast Stem Cells