Association analysis between the distributions of histone modifications and gene expression in the human embryonic stem cell

Su, Wei; Li, Qian‐Zhong; Zuo, Yongchun; Zhang, Lu-Qiang

doi:10.1016/j.gene.2015.08.041

Cited by 11 publications

(7 citation statements)

References 58 publications

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“…Thus, H3K9ac, H3K27me3 and H3K4me3 are more reliable information parameters than other HMs in H1-hESc, which consist with previous study [23]. Furthermore, we check the times that H3K9ac, H3K27me3, H3K4me3 and H3K36me3 appear together (shown in Figure 3B).…”

Section: Resultssupporting

confidence: 79%

“…The presences or absences of some TFs and HMs are correlated with gene expression levels [1, 16, 20, 23]. To better understand the relations between TFs (HMs) and gene expression levels, we construct log-linear model and non-linear SVR model for three immortalized human cell lines: H1-hESC, GM12878 and K562.…”

Section: Resultsmentioning

confidence: 99%

“…In order to further investigate the effects of TFs and HMs on prediction for genes in independent biological processes, we focus on the Gene Ontology biological processes [32, 33] for the high expression genes in the three cell lines (based on RPKM values, the top fifteen percent of all genes are selected as high expressed genes [3, 23]). Firstly, biological processes containing less than 30 genes are discarded, 1104, 1136 and 1070 sets of genes are remained, respectively, for H1-hESc, Gm12878 and K562 cell line.…”

Section: Resultsmentioning

confidence: 99%

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Estimating the effects of transcription factors binding and histone modifications on gene expression levels in human cells

Zhang

2017

Oncotarget

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Transcription factors and histone modifications are vital for the regulation of gene expression. Hence, to estimate the effects of transcription factors binding and histone modifications on gene expression, we construct a statistical model for the genome-wide 15 transcription factors binding data, 10 histone modifications profiles and DNase-I hypersensitivity data in three mammalian. Remarkably, our results show POLR2A and H3K36me3 can highly and consistently predict gene expression in three cell lines. And H3K4me3, H3K27me3 and H3K9ac are more reliable predictors than other histone modifications in human embryonic stem cells. Moreover, genome-wide statistical redundancies exist within and between transcription factors and histone modifications, and these phenomena may be caused by the regulation mechanism. In further study, we find that even though transcription factors and histone modifications offer similar effects on expression levels of genome-wide genes, the effects of transcription factors and histone modifications on predictive abilities are different for genes in independent biological processes.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Estimating the effects of transcription factors binding and histone modifications on gene expression levels in human cells

Zhang

2017

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“…Jumonji domain-containing protein 2C (JMJD2C), also known as KDM4C, could modulate transcription factors, establish global chromatin environments and regulate gene expression [9–11]. A number of evidences have suggested the association between JMJD2C protein and various tumors [12–15].…”

Section: Introductionmentioning

confidence: 99%

JMJD2C promotes colorectal cancer metastasis via regulating histone methylation of MALAT1 promoter and enhancing β-catenin signaling pathway

Song

et al. 2019

J Exp Clin Cancer Res

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BackgroundOur previous work demonstrated that lncRNA-MALAT1 was overexpressed in recurrent colorectal cancer (CRC) and metastatic sites in post-surgical patients. However, the upstream regulatory mechanism of MALAT1 is not well-defined. Histone demethylase JMJD2C holds great potential of epigenetic regulating mechanism in tumor diseases, especially the moderating effect on the promoter activity of targeted genes associated closely with tumor development. Therefore, we herein investigated whether JMJD2C could epigeneticly regulate the promoter activity of MALAT1 and the downstream β-catenin signaling pathway, thereby affecting the metastatic abilities of CRC cells.MethodsJMJD2C expressions in human CRC samples were detected by real-time PCR and immunohistochemistry staining. Gene silencing and overexpressing efficiencies of JMJD2C were confirmed by real-time PCR and western blot. The migration of CRC cells in vitro were tested by transwell and wound healing assays. The protein expression and cellular localization of JMJD2C and β-catenin were characterized by immunofluorescence staining and western blot. The histone methylation level of MALAT1 promoter region (H3K9me3 and H3K36me3) was tested by ChIP-PCR assays. The promoter activity of MALAT1 was detected by luciferase reporter assay. The expressions of MALAT1 and the downstream β-catenin signaling pathway related genes in CRC cells were detected by real-time PCR and western blot, respectively. The nude mice tail vein metastasis model was established to observe the effect of JMJD2C on the lung metastasis of CRC cells in vivo.ResultsOur present results indicated that histone demethylase JMJD2C was overexpressed in matched CRC tumor tissues of primary and metastatic foci, and CRC patients with lower JMJD2C expression in primary tumors had better prognosis with longer OS (Overall Survival). The following biological function observation suggested that JMJD2C promoted CRC metastasis in vitro and in vivo. Further molecular mechanism investigation demonstrated that JMJD2C protein translocated into the nuclear, lowered the histone methylation level of MALAT1 promoter in the sites of H3K9me3 and H3K36me3, up-regulated the expression of MALAT1, and enhanced the β-catenin signaling pathway in CRC cells.ConclusionOur data demonstrated that JMJD2C could enhance the metastatic abilities of CRC cells in vitro and in vivo by regulating the histone methylation level of MALAT1 promoter, thereby up-regulating the expression of MALAT1 and enhancing the activity of β-catenin signaling pathway, providing that JMJD2C might be a novel therapeutic target for CRC metastasis.

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“…It is well known that, histone modifications can regulate gene expression by establishing global chromatin environments [ 18 , 19 , 20 ], and these epigenetic changes in chromatin environments are the underlying causes of tumors development. The amino-terminal tails of histone are subjected to numerous reversible posttranslational modifications, such as phosphorylation [ 21 ], acetylation [ 22 ], ubiquitination [ 23 ], sumoylation [ 24 ], ADP ribosylation [ 25 ], and methylation [ 26 , 27 ].…”

Section: Origins and Properties Of Jmjd2cmentioning

confidence: 99%

Histone demethylase JMJD2C: epigenetic regulators in tumors

Zhang

Wang

et al. 2017

Oncotarget

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Histone methylation is one of the major epigenetic modifications, and various histone methylases and demethylases participate in the epigenetic regulating. JMJD2C has been recently identified as one of the histone lysine demethylases. As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes. JMJD2C was firstly found to involve in embryonic development and stem cell regulation. Afterwards, aberrant status of JMJD2C histone methylation was observed during the formation and development of various tumors, and it has been reported to play crucial roles in the progression of breast cancer, prostate carcinomas, osteosarcoma, blood neoplasms and so on, indicating that JMJD2C represents a promising anti-cancer target. In this review, we will focus on the research progress and prospect of JMJD2C in tumors, and provide abundant evidence for the functional application and therapeutic potential of targeting JMJD2C in tumors.

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Association analysis between the distributions of histone modifications and gene expression in the human embryonic stem cell

Cited by 11 publications

References 58 publications

Estimating the effects of transcription factors binding and histone modifications on gene expression levels in human cells

Estimating the effects of transcription factors binding and histone modifications on gene expression levels in human cells

JMJD2C promotes colorectal cancer metastasis via regulating histone methylation of MALAT1 promoter and enhancing β-catenin signaling pathway

Histone demethylase JMJD2C: epigenetic regulators in tumors

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