7 results on '"Guojia Xie"'
Search Results
2. UTX promotes hormonally responsive breast carcinogenesis through feed-forward transcription regulation with estrogen receptor
- Author
-
Zhengming Chen, Shumeng Liu, Youyi Zhang, Tong Jin, Guojia Xie, Yongfeng Shang, Jianguo Yang, Liyun He, Jing Liang, Wenmei Li, Bosen Xu, Luyang Sun, Xinhua Liu, Xia Yi, and Zhiyong Zhang
- Subjects
Transcriptional Activation ,0301 basic medicine ,Receptors, CXCR4 ,Cancer Research ,Carcinogenesis ,Estrogen receptor ,Breast Neoplasms ,Biology ,Transfection ,medicine.disease_cause ,Molecular oncology ,Metastasis ,Gene Knockout Techniques ,03 medical and health sciences ,Breast cancer ,Genetics ,medicine ,Humans ,Epigenetics ,Molecular Biology ,Histone Demethylases ,Regulation of gene expression ,Estrogen Receptor alpha ,Nuclear Proteins ,medicine.disease ,030104 developmental biology ,Tissue Array Analysis ,MCF-7 Cells ,Cancer research ,Female ,Estrogen receptor alpha - Abstract
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis. We demonstrated that UTX promotes the proliferation and migration of ER+ breast cancer cells. Interestingly, UTX itself is transactivated by ER, forming a feed-forward loop in the regulation of hormone response. Indeed, UTX is upregulated during ER+ breast cancer progression, and the expression level of UTX is positively correlated with that of CXCR4 and negatively correlated with the overall survival of ER+ breast cancer patients. Our study identified a feed-forward loop between UTX and ER in the regulation of hormonally responsive breast carcinogenesis, supporting the pursuit of UTX as an emerging therapeutic target for the intervention of certain ER+ breast cancer with specific epigenetic vulnerability.
- Published
- 2017
3. PAAT, a novel ATPase andtrans‐regulator of mitochondrial ABC transporters, is critically involved in the maintenance of mitochondrial homeostasis
- Author
-
Guojia Xie, Wenzhe Si, Xiaohan Yang, Lei Li, Xia Yi, Jianguo Yang, Wanjin Li, Jing Liang, Yongfeng Shang, Zhe Chen, Ruorong Yan, Luyang Sun, and Xiao Han
- Subjects
Amino Acid Transport System A ,biology ,Chemistry ,ATPase ,ABCB6 ,ATP-binding cassette transporter ,Oxidative phosphorylation ,Mitochondrion ,Biochemistry ,ABCB7 ,Mitochondria ,Cell biology ,Protein Transport ,Cytoplasm ,Genetics ,biology.protein ,Homeostasis ,Humans ,Inner mitochondrial membrane ,Molecular Biology ,Cells, Cultured ,Protein Binding ,Biotechnology - Abstract
ATP-binding cassette (ABC) transporters are implicated in a diverse range of physiological and pathophysiological processes, such as cholesterol and lipid transportation and multidrug resistance. Despite the considerable efforts made in understanding of the cellular function of ABC proteins, the regulation mechanism of this type of protein is still poorly defined. Here we report the identification and functional characterization of a novel ATPase protein, protein associated with ABC transporters (PAAT), in humans. PAAT contains a nucleotide-binding domain (NBD)-like domain and a signal for intramitochondrial sorting. We showed that PAAT is localized in both the cytoplasm and the mitochondria and has an intrinsic ATPase activity. PAAT physically interacts with the 3 known mitochondrial inner membrane ABC proteins, ABCB7, ABCB8, and ABCB10, but not ABCB1, ABCB6, or ABCG2, and functionally regulates the transport of ferric nutrients and heme biosynthesis. Significantly, PAAT deficiency promotes cell death, reduces mitochondrial potential, and sensitizes mitochondria to oxidative stress-induced DNA damages. Our experiments revealed that PAAT is a novel ATPase and a trans-regulator of mitochondrial ABC transporters that plays an important role in the maintenance of mitochondrial homeostasis and cell survival.
- Published
- 2014
4. Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks
- Author
-
Jing Liang, Yu Zhang, Shumeng Liu, Yongqing Liu, Bosen Xu, Yongfeng Shang, Shuai Yuan, Luyang Sun, Zhe Chen, Guojia Xie, Xiaohan Yang, Huajing Yu, and Wanjin Li
- Subjects
0301 basic medicine ,DNA Replication ,Biology ,Chromodomain ,Epigenesis, Genetic ,S Phase ,Histones ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Genetics ,MCM complex ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Epigenetics ,Chromatin Assembly Factor-1 ,Protein Methyltransferases ,Molecular Biology ,Hydro-Lyases ,CAF-1 ,Minichromosome Maintenance Proteins ,Lysine ,EZH2 ,Proteins ,Cell Biology ,General Medicine ,Histone-Lysine N-Methyltransferase ,Chromatin ,Cell biology ,030104 developmental biology ,Histone ,biology.protein ,Co-Repressor Proteins ,030217 neurology & neurosurgery ,DNA Damage ,Transcription Factors - Abstract
Faithful transmission or restoration of epigenetic information such as repressive histone modifications through generations is critical for the maintenance of cell identity. We report here that chromodomain Y-like protein (CDYL), a chromodomain-containing transcription corepressor, is physically associated with chromatin assembly factor 1 (CAF-1) and the replicative helicase MCM complex. We showed that CDYL bridges CAF-1 and MCM, facilitating histone transfer and deposition during DNA replication. We demonstrated that CDYL recruits histone-modifying enzymes G9a, SETDB1, and EZH2 to replication forks, leading to the addition of H3K9me2/3 and H3K27me2/3 on newly deposited histone H3. Significantly, depletion of CDYL impedes early S phase progression and sensitizes cells to DNA damage. Our data indicate that CDYL plays an important role in the transmission/restoration of repressive histone marks, thereby preserving the epigenetic landscape for the maintenance of cell identity.
- Published
- 2016
5. Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering
- Author
-
Jing Liang, Yongfeng Shang, Wanjin Li, Zhe Chen, Di Zhang, Ruorong Yan, Lin He, Yu Zhang, Luyang Sun, Guojia Xie, Xia Yi, Qian Li, Bosen Xu, Lei Li, Jianguo Yang, and Shumeng Liu
- Subjects
0301 basic medicine ,Epigenomics ,Hepatocyte Nuclear Factor 3-alpha ,DNA Repair ,Transcription, Genetic ,DNA polymerase ,DNA repair ,03 medical and health sciences ,chemistry.chemical_compound ,DNA repair complex ,Neoplasms ,Genetics ,Humans ,Epigenetics ,Promoter Regions, Genetic ,DNA Polymerase beta ,Binding Sites ,biology ,Estrogens ,DNA Methylation ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,DNA demethylation ,DNA Repair Enzymes ,chemistry ,DNA methylation ,biology.protein ,MCF-7 Cells ,DNA ,HeLa Cells - Abstract
FOXA1 functions in epigenetic reprogramming and is described as a 'pioneer factor'. However, exactly how FOXA1 achieves these remarkable biological functions is not fully understood. Here we report that FOXA1 associates with DNA repair complexes and is required for genomic targeting of DNA polymerase β (POLB) in human cells. Genome-wide DNA methylomes demonstrate that the FOXA1 DNA repair complex is functionally linked to DNA demethylation in a lineage-specific fashion. Depletion of FOXA1 results in localized reestablishment of methylation in a large portion of FOXA1-bound regions, and the regions with the most consistent hypermethylation exhibit the greatest loss of POLB and are represented by active promoters and enhancers. Consistently, overexpression of FOXA1 commits its binding sites to active DNA demethylation in a POLB-dependent manner. Finally, FOXA1-associated DNA demethylation is tightly coupled with estrogen receptor genomic targeting and estrogen responsiveness. Together, these results link FOXA1-associated DNA demethylation to transcriptional pioneering by FOXA1.
- Published
- 2016
6. Corepressor Protein CDYL Functions as a Molecular Bridge between Polycomb Repressor Complex 2 and Repressive Chromatin Mark Trimethylated Histone Lysine 27
- Author
-
Jing Liang, Bin Gui, Di Zhang, Yongfeng Shang, Yu Zhang, Guojia Xie, and Xiaohan Yang
- Subjects
Xenopus ,Polycomb-Group Proteins ,macromolecular substances ,DNA and Chromosomes ,complex mixtures ,Methylation ,Biochemistry ,Epigenesis, Genetic ,Histones ,Histone H3 ,Catalytic Domain ,Cell Line, Tumor ,Histone methylation ,Polycomb-group proteins ,Animals ,Humans ,Nucleosome ,Molecular Biology ,Hydro-Lyases ,Genetics ,biology ,Lysine ,fungi ,Proteins ,Methyltransferases ,Cell Biology ,Chromatin ,Nucleosomes ,ChIP-sequencing ,Cell biology ,Repressor Proteins ,Histone ,Gene Expression Regulation ,biology.protein ,bacteria ,PRC2 ,Co-Repressor Proteins - Abstract
Polycomb group proteins play essential roles in transcriptional regulation of multiple gene families involved in various pathophysiological processes. It is believed that Polycomb Repressive Complex 2 (PRC2) is targeted to chromatin by the EED subunit to methylate histone H3 lysine 27 (H3K27), leading to a repressive chromatin state that inhibits gene expression. Here we report that the chromodomain-containing protein CDYL specifically recognizes di- and tri-methylated H3K27 (H3K27me2 and H3K27me3) and directly interacts with EZH2, the catalytic subunit of PRC2. We show that CDYL dramatically enhances the methyltransferase activity of PRC2 toward oligonucleosome substrates in vitro. Genome-wide analysis of CDYL targets by ChIP sequencing revealed that CDYL and PRC2 share a number of genomic targets. CDYL is required for chromatin targeting and maximal enzymatic activity of PRC2 at their common target sites. Our experiments indicate that CDYL functions as a molecular bridge between PRC2 and the repressive chromatin mark H3K27me3, forming a positive feedback loop to facilitate the establishment and propagation of H3K27me3 modifications along the chromatin.
- Published
- 2011
7. SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer
- Author
-
Luyang Sun, Wanjin Li, Hongquan Zhang, Lin He, Dengfeng Cao, Peiyan Wang, Lei Li, Wenzhe Si, Zhe Chen, Fei Pei, Guojia Xie, Yongfeng Shang, Ruorong Yan, Jing Liang, Xiao Han, Zhongwu Li, and Liandi Lei
- Subjects
Angiogenesis ,Breast Neoplasms ,Cell Cycle Proteins ,F-box protein ,Metastasis ,Breast cancer ,Ubiquitin ,Genetics ,medicine ,Humans ,Neoplasm Metastasis ,Loss function ,Homeodomain Proteins ,biology ,Neovascularization, Pathologic ,F-Box Proteins ,Tumor Suppressor Proteins ,NF-kappa B ,Ubiquitination ,medicine.disease ,Research Papers ,Ubiquitin ligase ,Gene Expression Regulation, Neoplastic ,Multiprotein Complexes ,Immunology ,Proteolysis ,biology.protein ,Cancer research ,MCF-7 Cells ,Female ,Signal transduction ,Developmental Biology ,Signal Transduction - Abstract
Loss of function/dysregulation of inhibitor of growth 4 (ING4) and hyperactivation of NF-κB are frequent events in many types of human malignancies. However, the molecular mechanisms underlying these remarkable aberrations are not understood. Here, we report that ING4 is physically associated with JFK. We demonstrated that JFK targets ING4 for ubiquitination and degradation through assembly of an Skp1–Cul1–F-box (SCF) complex. We showed that JFK-mediated ING4 destabilization leads to the hyperactivation of the canonical NF-κB pathway and promotes angiogenesis and metastasis of breast cancer. Significantly, the expression of JFK is markedly up-regulated in breast cancer, and the level of JFK is negatively correlated with that of ING4 and positively correlated with an aggressive clinical behavior of breast carcinomas. Our study identified SCFJFK as a bona fide E3 ligase for ING4 and unraveled the JFK–ING4–NF-κB axis as an important player in the development and progression of breast cancer, supporting the pursuit of JFK as a potential target for breast cancer intervention.
- Published
- 2015
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.