Polycomb group (PcG) proteins are a family of epigenetic regulators responsible for the repression of genes in proliferation and differentiation of stem cells. PcG protein complex consists of two important epigenetic regulators: PRC1 (polycomb repressive complex 1) and PRC2 (polycomb repressive complex 2). In order to further understand the functions of PcG proteins in stem cell growth and differentiation, we review the PcG protein composition, PcG protein localization in the target gene, PcG protein recruitment, and the functions of PcG proteins in the development of stem cells.
Cell Differentiation ; physiology ; Cell Proliferation ; Humans ; Polycomb Repressive Complex 1 ; metabolism ; physiology ; Polycomb Repressive Complex 2 ; metabolism ; physiology ; Polycomb-Group Proteins ; metabolism ; physiology ; Stem Cells ; cytology ; metabolism

Polycomb Group Proteins (PcG) are a family of epigenetic regulators responsible for the repression of an array of genes important in development and cell fate specification. PcG proteins complex to form two types of epigenetic regulators: Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2). Although the mechanisms regulating PRC2 recruitment and activity in mammals remain poorly understood, recent work has identified a non-canonical PRC2 in mouse embryonic stem cells (mESC) with unique activities required for repression of PRC2 target genes and necessary for mESC differentiation and somatic cell reprogramming. Here we review the functions of PRC2 in embryonic stem cells and explore the role of the newly identified mESC specific PRC2 regulatory subunits Jarid2 (jumonji, AT rich interactive domain 2), Mtf2 (metal response element binding transcription factor 2) and esPRC2p48.
Animals ; Cell Differentiation ; genetics ; Embryonic Stem Cells ; cytology ; metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Histones ; genetics ; metabolism ; Mice ; Nerve Tissue Proteins ; genetics ; metabolism ; Polycomb Repressive Complex 2 ; Polycomb-Group Proteins ; Protein Binding ; genetics ; Protein Subunits ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism

Antineoplastic Agents ; therapeutic use ; Enhancer of Zeste Homolog 2 Protein ; Epigenesis, Genetic ; Histone Deacetylase Inhibitors ; therapeutic use ; Humans ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Lymphoma ; classification ; drug therapy ; genetics ; metabolism ; MicroRNAs ; metabolism ; Phenotype ; Polycomb Repressive Complex 2 ; metabolism ; Polycomb-Group Proteins ; metabolism

Transcriptional regulation of a gene is not always correlated with genetic information inherited from parents because the transcription of specific genes is often governed by the modification of chromatin structure. The study of transcriptional regulation by modifying chromatin structure is well-known as "epigenetics". Several methods involved in the modification of chromatin structure have been developed in the mammalian species during evolution. Among those methods, methylations of specific DNA region or histone are often used to control specific gene transcription. Therefore, understanding the activity of proteins involved in DNA or histone methylation is an initial step to control the transcriptional activity of a specific gene. Polycomb group (PcG) proteins were known to be repressors of transcription of a specific gene by creating and maintaining methylation or ubiquitination of the specific region of histone. Dependent on the target histone, the activity of PcG proteins effects on the development of specific lineage cells or the activity of specific cell types. In this review, the function, expression and activity of PcG proteins related with the development or activation of T cells are discussed.
Chromatin ; DNA ; Epigenomics ; Genes, vif ; Histone Code ; Histones ; Humans ; Methylation ; Parents ; Polycomb-Group Proteins ; Proteins ; T-Lymphocytes ; Ubiquitin ; Ubiquitination

The establishment and maintenance of mammary epithelial cell identity depends on the activity of a group of proteins, collectively called maintenance proteins, that act as epigenetic regulators of gene transcription through DNA methylation, histone modification, and chromatin remodeling. Increasing evidence indicates that dysregulation of these crucial proteins may disrupt epithelial cell integrity and trigger breast tumor initiation. Therefore, we explored in silico the expression pattern of a panel of 369 genes known to be involved in the establishment and maintenance of epithelial cell identity and mammary gland remodeling in cell subpopulations isolated from normal human mammary tissue and selectively enriched in their content of bipotent progenitors, committed luminal progenitors, and differentiated myoepithelial or differentiated luminal cells. The results indicated that, compared to bipotent cells, differentiated myoepithelial and luminal subpopulations were both characterized by the differential expression of 4 genes involved in cell identity maintenance: CBX6 and PCGF2, encoding proteins belonging to the Polycomb group, and SMARCD3 and SMARCE1, encoding proteins belonging to the Trithorax group. In addition to these common genes, the myoepithelial phenotype was associated with the differential expression of HDAC1, which encodes histone deacetylase 1, whereas the luminal phenotype was associated with the differential expression of SMARCA4 and HAT1, which encode a Trithorax protein and histone acetylase 1, respectively. The luminal compartment was further characterized by the overexpression of ALDH1A3 and GATA3, and the down-regulation of NOTCH4 and CCNB1, with the latter suggesting a block in cell cycle progression at the G2 phase. In contrast, myoepithelial differentiation was associated with the overexpression of MYC and the down-regulation of CCNE1, with the latter suggesting a block in cell cycle progression at the G1 phase.
Breast ; Breast Neoplasms ; genetics ; Cell Differentiation ; Cell Transformation, Neoplastic ; genetics ; Down-Regulation ; Epigenesis, Genetic ; Epithelial Cells ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Regulator ; Humans ; Mammary Glands, Human ; Polycomb-Group Proteins

OBJECTIVE: To establish the drug-resistant cell lines of hepatocellular carcinoma (HCC) induced by sorafenib, and to screen out the high expression genes in drug-resistant cell lines of HCC induced by sorafenib, then to explore the genes related to sorafenib resistance in hepatocellular carcinoma. METHODS: The human PLC and Huh7 cell lines were obtained, then the PLC and Huh7 drug-resistant cell lines were induced with sorafenib by using intermittent induction in vitro. CCK8 assay was used to detect the IC50 value of sorafenib for evaluation of drug sensitivity of hepatocellular carcinoma cell lines in PLC and Huh7. All the up regulated genes in PLC and Huh7 drug-resistant cell lines induced by sorafenib were screened out using high-throughput cDNA sequencing (RNA-Seq), Ualcan database was used to analyze the correlations between the up regulated genes in PLC and Huh7 drug-resistant cell lines induced and four clinical biological characteristics of hepatocellular carcinoma, including the gene expressions between normal samples and tumor samples, tumor stage, tumor grade, and patient overall survival, to find the genes that might be involved in the mechanism of sorafenib resistance of hepatocellular carcinoma. RESULTS: All the up regulated genes detected by the using high-throughput cDNA sequencing (RNA-Seq) in PLC and Huh7 drug-resistant cell lines were further screened out by following conditions:(1) genes co-expressed in PLC and Huh7 drug-resistant cells induced by sorafenib, (2) the fold change was more than 4 times and the difference was statistically significant (P <0.05), the top 12 up regulated genes in PLC and Huh7 drug-resistant cell lines were found, which were TPSG1, CBX4, CLC, CLEC18C, LGI4, F2RL1, S100A6, HABP2, C15ORF48, ZG16, FOLH1, and EPCAM. Compared with the correlations between the twelve genes and the clinical biological characteristics by Ualcan database, the potentially significant gene CBX4 was screened out. CONCLUSION The human PLC and Huh7 drug-resistant cell lines of hepatocellular carcinoma induced by sorafenib were successfully established. CBX4, the gene related to sorafenib resistance in hepatocellular carcinoma, was screened out by the high-throughput cDNA sequencing (RNA-Seq) and further analysis using Ualcan database, which is providing a powerful basis for further research on the mechanism of sorafenib resistance of hepatocellular carcinoma.
Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Humans ; Ligases ; Liver Neoplasms/drug therapy* ; Polycomb-Group Proteins ; Serine Endopeptidases ; Sorafenib/therapeutic use*

OBJECTIVE: Endometrial carcinoma is the most common gynecological malignant disease in industrialized countries. However, the molecular bases for endometrial tumoriogenesis are not clearly elucidated. Our hypothesis is that there may be some difference in gene expression patterns between normal endometrium and endometrial cancer lesion. In this study, we analyzed the difference of gene expression profile with cDNA microarray. METHODS: Normal endometrial tissues and cancer lesions were gathered from three patient with endometrioid endometrial cancer. cDNA microarray technique (KNU 4.8K chip) was applied to screen the different gene expression profiles. RESULTS: Many genes such as interleukin-1 receptor-associated kinase 1 (IRAK1), bifunctional apoptosis regulator (BFAR), paraneoplastic antigen MA2 (PNMA2), zinc finger protein 257 (ZNF257), ras homolog gene family, member F (in filopodia) (ARHF), cell division cycle 27 (CDC27) were over-expressed in the endometrial cancer tissue. The genes were down-regulated in the endometrial cancer samples included fibronectin 1 (FN1), meiotic checkpoint regulator (MCPR), transforming growth factor beta-stimulated protein TSC-22 (TSC22), programmed cell death 4 (neoplastic transformation inhibitor) (PDCD4), transcript variant 2, matrix metalloproteinase 2 (MMP2), insulin-like growth factor binding protein 4 (IGFBP4), retinoblastoma binding protein 7 (RBBP7), insulin-like growth factor binding protein 3 (IGFBP3), downregulated in ovarian cancer 1 (DOC1). CONCLUSION: The result of this analysis supports the hypothesis that the endometrial cancer tissue has distinct gene expression profile from normal endometium. But, the vaildation of gene expression with RT-PCR and the further study are needed.
Apoptosis ; Cell Cycle ; Cell Death ; Developed Countries ; DNA, Complementary* ; Endometrial Neoplasms* ; Endometrium ; Female ; Fibronectins ; Gene Expression* ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Interleukin-1 Receptor-Associated Kinases ; Matrix Metalloproteinase 2 ; Oligonucleotide Array Sequence Analysis* ; Ovarian Neoplasms ; Retinoblastoma-Binding Protein 7 ; Transcriptome* ; Transforming Growth Factors ; Zinc Fingers

During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.
Animals ; Breast Neoplasms ; genetics ; pathology ; physiopathology ; Cell Transformation, Neoplastic ; Chromatin ; genetics ; metabolism ; Epigenesis, Genetic ; physiology ; Epithelial Cells ; cytology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Histone-Lysine N-Methyltransferase ; Humans ; Mammary Glands, Animal ; cytology ; growth & development ; Mammary Glands, Human ; cytology ; growth & development ; Myeloid-Lymphoid Leukemia Protein ; genetics ; physiology ; Polycomb-Group Proteins ; genetics ; physiology ; Receptors, Estrogen ; metabolism

OBJECTIVETo study the regulatory rolesof SIRT1 on EZH2 expression and the further effects on EZH 2’ s repression of target gene expression.

METHODSThe stable SIRT1 RNAi and Control RNAi HeLa cells were established by infection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation(ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells.

RESULTSWestern blot results showed that EZH2 protein level increased upon SIRT1 depletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter regionof EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases.

CONCLUSIONSDepletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expression.

DNA-Binding Proteins ; analysis ; chemistry ; physiology ; Enhancer of Zeste Homolog 2 Protein ; Gene Expression Regulation ; HeLa Cells ; Humans ; Polycomb Repressive Complex 2 ; Repressor Proteins ; physiology ; Sirtuin 1 ; antagonists & inhibitors ; physiology ; Transcription Factors ; analysis ; chemistry ; physiology

OBJECTIVETo investigate the Bmi1 protein level in human colorectal cancer specimen and associated clinicopathological parameters, and to determine the influence of Bmi1 on the proliferation and apoptosis of colorectal cancer cells.

METHODSBmi1 protein level was assessed in 85 patients with colorectal cancer and adjacent normal tissue by immunohistochemistry. SW480 cells were transfected with Bmi siRNA plasmid. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of Bmi1 and Bcl-2 were measured by Western blot.

RESULTSThe positive rate of Bmi1 expression in colorectal cancer tissues was 56.5%(48/85), significantly higher than that in the adjacent noncancerous tissues[17.6%(15/85), P<0.05)]. It was found that the overexpression of Bmi1 was associated with degree of differentiation, status of lymph nodes metastasis, and TNM staging in colorectal cancer(P<0.05). After transfection of SW480 with Bmi1 siRNA, the cell proliferation was inhibited and the apoptosis was significant. The cell proliferation inhibitory rates were 13.1%, 16.5%, and 18.3% at 24 h, 48 h and 72 h after transfection. The apoptotic rates were 15.7%, 45.6%, 40.2%, respectively. Expression of Bmi1 was downregulated after 48 h, as was that of Bcl-2.

CONCLUSIONSBmi1 expression is associated with the clinicopathological characteristics of colorectal cancer. Blockade of Bmi1 can inhibit the proliferation and accelerate the apoptosis of colorectal cancer cells.

Aged ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Polycomb Repressive Complex 1 ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism