Effects of increased YY2 expression on heart development
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PROVIDER: PRJNA608301 | ENA |
REPOSITORIES: ENA
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Project description:Yin Yang 2 (YY2) is a member of the Yin Yang family of transcription factors. Although the bioactivity of YY2 has been previously studied, its role in cardiovascular diseases is not known. We observed the increased expression of YY2 in failing human hearts compared with control hearts, raising the question of whether YY2 is involved in the pathogenesis of cardiomyopathy. To investigate the potential contribution of YY2 to the development of cardiomyopathy, we crossed two transgenic (Tg) mouse lines, pCAG-YY2-Tg+ and -MHC-Cre, to generate two independent double transgenic (dTg) mouse lines in which the conditional cardiomyocyte-specific expression of YY2 driven by the -MHC promoter was mediated by Cre recombinase, starting at embryonic day 9.0. In dTg mice, we observed partial embryonic lethality and hearts with defective cardiomyocyte proliferation. Surviving dTg mice from both lines developed cardiomyopathy and heart failure that occurred with aging, showing different degrees of severity that were associated with the level of transgene expression. The development of cardiomyopathy was accompanied by increased levels of cardiac disease markers, apoptosis, and cardiac fibrosis. Our studies further revealed that the Cre-mediated cardiomyocyte-specific increase in YY2 expression led to increased levels of Beclin 1 and LC3II, indicating that YY2 is involved in mediating autophagic activity in mouse hearts in vivo. Also, compared with control hearts, dTG mouse hearts showed increased JNK activity. Because autophagy and JNK activity are important for maintaining cardiac homeostasis, the dysregulation of these signaling pathways may contribute to YY2-induced cardiomyopathy and heart failure in vivo.
2020-02-25 | GSE145808 | GEO
Project description:Yin Yang 1 (YY1) is a critical transcription factor controlling cell proliferation, development and DNA damage responses. Although two homologous Drosophila YY family members (pleiohomeotic (pho)) and pleiohomeotic-like (phol)) are redundant, the functional significance of a recently described mammalian YY1-like gene (YY2) is unknown. Using microarray and gene set enrichment analysis (GSEA), we found that lentiviral constructs containing short hairpin loop YY1- and YY2-specific inhibitory RNAs (shYY1 and shYY2) caused significant changes in both redundant and distinguishable expression patterns. Ribosomal protein genes were the most significant gene set up-regulated by both shYY1 and shYY2, although combined shYY1/shYY2 knockdowns were not additive. In contrast, shYY2 reversed anti-proliferative effects of shYY1 on E2F target genes, and shYY2 particularly altered UV damage response, platelet-specific genes and mitochondrial function genes. The most YY2-specific gene was the platelet glycoprotein CD36 whose ligand is thrombospondin - a key UV response gene. We found that decreases in YY1 or YY2 caused inverse changes in UV sensitivity, and that their combined loss reversed their respective individual effects. Taken together, our studies show that YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously thought to uniquely respond to YY1. Functions of thrombospondin and CD36 in inflammation, atherogenesis, innate immunity and malaria pathogenesis reveal new potential regulatory roles for YY1 and YY2. Four treatment groups were used that included control vector (pLKO) virus, shYY1, shYY2 and shYY1 combined with shYY2. Three replicas were performed for all except shYY2, where we performed four replicas. Target gene comparison of YY1 And YY2 homologous genes.
2010-03-08 | E-GEOD-14964 | biostudies-arrayexpress
Project description:Yin Yang 1 (YY1) is a critical transcription factor controlling cell proliferation, development and DNA damage responses. Although two homologous Drosophila YY family members (pleiohomeotic (pho)) and pleiohomeotic-like (phol)) are redundant, the functional significance of a recently described mammalian YY1-like gene (YY2) is unknown. Using microarray and gene set enrichment analysis (GSEA), we found that lentiviral constructs containing short hairpin loop YY1- and YY2-specific inhibitory RNAs (shYY1 and shYY2) caused significant changes in both redundant and distinguishable expression patterns. Ribosomal protein genes were the most significant gene set up-regulated by both shYY1 and shYY2, although combined shYY1/shYY2 knockdowns were not additive. In contrast, shYY2 reversed anti-proliferative effects of shYY1 on E2F target genes, and shYY2 particularly altered UV damage response, platelet-specific genes and mitochondrial function genes. The most YY2-specific gene was the platelet glycoprotein CD36 whose ligand is thrombospondin - a key UV response gene. We found that decreases in YY1 or YY2 caused inverse changes in UV sensitivity, and that their combined loss reversed their respective individual effects. Taken together, our studies show that YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously thought to uniquely respond to YY1. Functions of thrombospondin and CD36 in inflammation, atherogenesis, innate immunity and malaria pathogenesis reveal new potential regulatory roles for YY1 and YY2.
2010-02-28 | GSE14964 | GEO
Project description:The effects of NAT10 on heart development
| PRJNA1144453 | ENA
Project description:The Yin Yang 2 (YY2) gene encodes a zinc finger transcription factor that is not well characterized, yet. By using chromatin immunoprecipitations combined with whole-genome human promoter microarray (ChIP-chip) in HEK293 cells, we identified a multiplicity of YY2-bound annotated promoters as well as additional chromosomal regions. Interestingly, gene ontology analyses linked YY2 to fundamental biological pathways associated to cancer and developmental processes. Identification of YY2 target genes in HEK293 cells in vivo
2013-06-16 | E-GEOD-22599 | biostudies-arrayexpress
Project description:The effects of WTAP on heart development [WTAPCKO]
| PRJNA943502 | ENA
Project description:The effects of NAT10 on heart development in mice
| PRJNA1254208 | ENA
Project description:We report the application of next generation sequencing for high-throughput profiling of Yin Yang 2 (YY2) binding sites in mammalian Trophectoderm Stem cells. Sequencing of chromatin obtained in chromatin-immunoprecipitation (ChIP) assays carried out with αYY2 serum yielded over ten million sequence reads. Peak finding allowed us allowed us to identify a limited number of chromatin targets for YY2. Putative binding sites were validated in regular ChIP assays and gene expression of a few genes nearby was altered in the absence of Yy2. This study provides a framework to understand the role of YY2 in diverse mammalian cell populations.
2016-05-03 | GSE80824 | GEO
Project description:The Yin Yang 2 (YY2) gene encodes a zinc finger transcription factor that is not well characterized, yet. By using chromatin immunoprecipitations combined with whole-genome human promoter microarray (ChIP-chip) in HEK293 cells, we identified a multiplicity of YY2-bound annotated promoters as well as additional chromosomal regions. Interestingly, gene ontology analyses linked YY2 to fundamental biological pathways associated to cancer and developmental processes.
2013-06-16 | GSE22599 | GEO
Project description:Yin Yang 1 (YY1) is a multifunctional DNA-binding transcription factor shown to be critical in a variety of biological processes, and its activity and function have been shown to be regulated by multitude of mechanisms, which include but are not limited to post-translational modifications (PTMs), its associated proteins and cellular localization. YY2, the paralog of YY1 in mouse and human, has been proposed to function redundantly or oppositely in a context specific manner compared to YY1. Despite its functional importance, how YY2’s DNA binding activity and function is regulated, particularly by PTMs, remains completely unknown. Here we report the first PTM with functional characterization on YY2, namely lysine 247 mono-methylation (K247me1), which was found to be dynamically regulated by SET7/9 and LSD1 both in vitro and in cultured cells. Functional study revealed that SET7/9-mediated YY2 methylation regulated its DNA-binding activity in vitro and association with chromatin examined by ChIP-seq (chromatin immunoprecipitation coupled with sequencing) in cultured cells. Knockout of YY2, SET7/9 or LSD1 by CRISPR (clustered, regularly interspaced, short palindromic repeats) /Cas9-mediated gene editing followed by RNA-seq revealed that a subset of genes was positively-regulated by YY2 and SET7/9, but negatively-regulated by LSD1, which were enriched with genes involved in cell proliferation regulation. Importantly, YY2-regulated gene transcription, cell proliferation and tumor growth were dependent, at least partially, on YY2 K247 methylation. Finally, somatic mutations on YY2 found in cancer, which are in close proximity to K247, altered its methylation, DNA binding activity and gene transcription it controls. Our findings revealed the first PTM with functional implications imposed on YY2 protein, and linked YY2 methylation with its biological functions.
2018-02-13 | GSE76856 | GEO