Scholars@Duke
Zhong Chen

Zhong Chen

Assistant Professor in Pathology
Pathology
zhong.chen128@duke.edu
GSRB I, RM1027B, Box #103864, 905 South LaSalle Steet, Durham, NC 27710
GSRB I, RM1027B, Box #103864, 905 South LaSalle Steet, Durham, NC 27710
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Selected Publications

Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.

Journal Article Nat Commun · June 7, 2022 Knowledge gaps remain on how nucleosome organization and dynamic reorganization are governed by specific pioneer factors in a genome-wide manner. In this study, we generate over three billons of multi-omics sequencing data to exploit dynamic nucleosome lan ... Full text Open Access Link to item Cite

Phosphorylated MED1 links transcription recycling and cancer growth.

Journal Article Nucleic Acids Res · May 6, 2022 Mediator activates RNA polymerase II (Pol II) function during transcription, but it remains unclear whether Mediator is able to travel with Pol II and regulate Pol II transcription beyond the initiation and early elongation steps. By using in vitro and in ... Full text Link to item Cite

Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling.

Journal Article Nat Commun · November 3, 2021 RNA Polymerase II (Pol II) transcriptional recycling is a mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of putati ... Full text Link to item Cite

Prostate Cancer Cell Phenotypes Remain Stable Following PDE5 Inhibition in the Clinically Relevant Range.

Journal Article Transl Oncol · September 2020 Widespread cGMP-specific phosphodiesterase 5 (PDE5) inhibitor use in male reproductive health and particularly in prostate cancer patients following surgery has generated interest in how these drugs affect the ability of residual tumor cells to proliferate ... Full text Link to item Cite

Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.

Journal Article Cancer Res · June 15, 2020 The androgen receptor (AR) is a critical therapeutic target in prostate cancer that responds to antagonists in primary disease, but inevitably becomes reactivated, signaling onset of the lethal castration-resistant prostate cancer (CRPC) stage. Epigenomic ... Full text Link to item Cite

Molecular determinants for enzalutamide-induced transcription in prostate cancer.

Journal Article Nucleic Acids Res · November 4, 2019 Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. ... Full text Open Access Link to item Cite

Chromatin-associated APC regulates gene expression in collaboration with canonical WNT signaling and AP-1.

Journal Article Oncotarget · July 27, 2018 Mutation of the APC gene occurs in a high percentage of colorectal tumors and is a central event driving tumor initiation in the large intestine. The APC protein performs multiple tumor suppressor functions including negative regulation of the canonical WN ... Full text Open Access Link to item Cite

Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13.

Journal Article Proc Natl Acad Sci U S A · June 26, 2018 The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting ther ... Full text Link to item Cite

Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1.

Journal Article Nucleic Acids Res · September 19, 2016 The compaction of nucleosomal structures creates a barrier for DNA-binding transcription factors (TFs) to access their cognate cis-regulatory elements. Pioneer factors (PFs) such as FOXA1 are able to directly access these cis-targets within compact chromat ... Full text Link to item Cite

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

Journal Article Nucleic Acids Res · May 19, 2016 Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 ... Full text Link to item Cite

Transcriptome regulation and chromatin occupancy by E2F3 and MYC in mice.

Journal Article Sci Data · February 16, 2016 E2F3 and MYC are transcription factors that control cellular proliferation. To study their mechanism of action in the context of a regenerating tissue, we isolated both proliferating (crypts) and non-dividing (villi) cells from wild-type and Rb depleted sm ... Full text Link to item Cite

Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes.

Journal Article Nat Genet · October 2015 Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs a ... Full text Link to item Cite

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.

Journal Article Nat Commun · September 16, 2015 Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find ... Full text Link to item Cite

Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.

Journal Article Nat Cell Biol · August 2015 Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells ... Full text Link to item Cite

Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.

Journal Article EMBO J · February 12, 2015 Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific ... Full text Link to item Cite

Three-tiered role of the pioneer factor GATA2 in promoting androgen-dependent gene expression in prostate cancer.

Journal Article Nucleic Acids Res · April 2014 In prostate cancer, androgen receptor (AR) binding and androgen-responsive gene expression are defined by hormone-independent binding patterns of the pioneer factors FoxA1 and GATA2. Insufficient evidence of the mechanisms by which GATA2 contributes to thi ... Full text Link to item Cite

Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.

Journal Article Nat Commun · June 7, 2022 Knowledge gaps remain on how nucleosome organization and dynamic reorganization are governed by specific pioneer factors in a genome-wide manner. In this study, we generate over three billons of multi-omics sequencing data to exploit dynamic nucleosome lan ... Full text Open Access Link to item Cite

Phosphorylated MED1 links transcription recycling and cancer growth.

Journal Article Nucleic Acids Res · May 6, 2022 Mediator activates RNA polymerase II (Pol II) function during transcription, but it remains unclear whether Mediator is able to travel with Pol II and regulate Pol II transcription beyond the initiation and early elongation steps. By using in vitro and in ... Full text Link to item Cite

Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling.

Journal Article Nat Commun · November 3, 2021 RNA Polymerase II (Pol II) transcriptional recycling is a mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of putati ... Full text Link to item Cite

Prostate Cancer Cell Phenotypes Remain Stable Following PDE5 Inhibition in the Clinically Relevant Range.

Journal Article Transl Oncol · September 2020 Widespread cGMP-specific phosphodiesterase 5 (PDE5) inhibitor use in male reproductive health and particularly in prostate cancer patients following surgery has generated interest in how these drugs affect the ability of residual tumor cells to proliferate ... Full text Link to item Cite

Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors.

Journal Article Cancer Res · June 15, 2020 The androgen receptor (AR) is a critical therapeutic target in prostate cancer that responds to antagonists in primary disease, but inevitably becomes reactivated, signaling onset of the lethal castration-resistant prostate cancer (CRPC) stage. Epigenomic ... Full text Link to item Cite

Molecular determinants for enzalutamide-induced transcription in prostate cancer.

Journal Article Nucleic Acids Res · November 4, 2019 Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. ... Full text Open Access Link to item Cite

Chromatin-associated APC regulates gene expression in collaboration with canonical WNT signaling and AP-1.

Journal Article Oncotarget · July 27, 2018 Mutation of the APC gene occurs in a high percentage of colorectal tumors and is a central event driving tumor initiation in the large intestine. The APC protein performs multiple tumor suppressor functions including negative regulation of the canonical WN ... Full text Open Access Link to item Cite

Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13.

Journal Article Proc Natl Acad Sci U S A · June 26, 2018 The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting ther ... Full text Link to item Cite

Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1.

Journal Article Nucleic Acids Res · September 19, 2016 The compaction of nucleosomal structures creates a barrier for DNA-binding transcription factors (TFs) to access their cognate cis-regulatory elements. Pioneer factors (PFs) such as FOXA1 are able to directly access these cis-targets within compact chromat ... Full text Link to item Cite

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

Journal Article Nucleic Acids Res · May 19, 2016 Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 ... Full text Link to item Cite

Transcriptome regulation and chromatin occupancy by E2F3 and MYC in mice.

Journal Article Sci Data · February 16, 2016 E2F3 and MYC are transcription factors that control cellular proliferation. To study their mechanism of action in the context of a regenerating tissue, we isolated both proliferating (crypts) and non-dividing (villi) cells from wild-type and Rb depleted sm ... Full text Link to item Cite

Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes.

Journal Article Nat Genet · October 2015 Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs a ... Full text Link to item Cite

Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.

Journal Article Nat Commun · September 16, 2015 Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find ... Full text Link to item Cite

Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.

Journal Article Nat Cell Biol · August 2015 Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells ... Full text Link to item Cite

Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.

Journal Article EMBO J · February 12, 2015 Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific ... Full text Link to item Cite

Three-tiered role of the pioneer factor GATA2 in promoting androgen-dependent gene expression in prostate cancer.

Journal Article Nucleic Acids Res · April 2014 In prostate cancer, androgen receptor (AR) binding and androgen-responsive gene expression are defined by hormone-independent binding patterns of the pioneer factors FoxA1 and GATA2. Insufficient evidence of the mechanisms by which GATA2 contributes to thi ... Full text Link to item Cite

Computational analysis reveals a correlation of exon-skipping events with splicing, transcription and epigenetic factors.

Journal Article Nucleic Acids Res · March 2014 Alternative splicing (AS), in higher eukaryotes, is one of the mechanisms of post-transcriptional regulation that generate multiple transcripts from the same gene. One particular mode of AS is the skipping event where an exon may be alternatively excluded ... Full text Link to item Cite

Integrated analysis identifies a class of androgen-responsive genes regulated by short combinatorial long-range mechanism facilitated by CTCF.

Journal Article Nucleic Acids Res · June 2012 Recently, much attention has been given to elucidate how long-range gene regulation comes into play and how histone modifications and distal transcription factor binding contribute toward this mechanism. Androgen receptor (AR), a key regulator of prostate ... Full text Link to item Cite

Definition of a FoxA1 Cistrome that is crucial for G1 to S-phase cell-cycle transit in castration-resistant prostate cancer.

Journal Article Cancer Res · November 1, 2011 The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G₂ to M-phase cell-cycle ... Full text Link to item Cite

CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability.

Journal Article Cancer Res · July 15, 2011 The cell-cycle G(2)-M phase gene UBE2C is overexpressed in various solid tumors including castration-resistant prostate cancer (CRPC). Our recent studies found UBE2C to be a CRPC-specific androgen receptor (AR) target gene that is necessary for CRPC growth ... Full text Link to item Cite

Phospho-MED1-enhanced UBE2C locus looping drives castration-resistant prostate cancer growth.

Journal Article EMBO J · May 10, 2011 The UBE2C oncogene is overexpressed in many types of solid tumours including the lethal castration-resistant prostate cancer (CRPC). The underlying mechanisms causing UBE2C gene overexpression in CRPC are not fully understood. Here, we show that CRPC-speci ... Full text Link to item Cite

Histone modifications and chromatin organization in prostate cancer.

Journal Article Epigenomics · August 2010 Epigenetic mechanisms, including histone modifications, nucleosomal remodeling and chromosomal looping, contribute to the onset and progression of prostate cancer. Recent technical advances significantly increase our understanding of the genome-wide epigen ... Full text Link to item Cite

Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping.

Journal Article Genome Res · June 2010 The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-range epigene ... Full text Link to item Cite

[The role of DNA methylation in the pathogenesis of adult idiopathic thrombocytopenic purpura].

Journal Article Zhonghua Nei Ke Za Zhi · March 2010 OBJECTIVE: To explore the role of DNA methylation in pathogenesis of adult idiopathic thrombocytopenic purpura (ITP). METHODS: We measured DNA methyltransferases (DNMTs) 1, 3A and 3B mRNA expression in peripheral blood mononuclear cells of 48 adult ITP pat ... Link to item Cite

Transcriptional regulation of survivin by c-Myc in BCR/ABL-transformed cells: implications in anti-leukaemic strategy.

Journal Article J Cell Mol Med · August 2009 BCR/ABL can cause chronic myelogenous leukaemia (CML) in part by altering the transcription of specific genes with growth- and/or survival-promoting functions. Recently, BCR/ABL has been shown to activate survivin, an important regulator of cell growth and ... Full text Link to item Cite

Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.

Journal Article Cell · July 23, 2009 The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. W ... Full text Link to item Cite

Overexpression of cell surface cytokeratin 8 in multidrug-resistant MCF-7/MX cells enhances cell adhesion to the extracellular matrix.

Journal Article Neoplasia · November 2008 Accumulating evidence suggests that multiple complex mechanisms may be involved, simultaneously or complementarily, in the emergence and development of multidrug resistance (MDR) in various cancers. Cell adhesion-mediated MDR is one such mechanism. In the ... Full text Link to item Cite

Decreased DNA methyltransferase 3A and 3B mRNA expression in peripheral blood mononuclear cells and increased plasma SAH concentration in adult patients with idiopathic thrombocytopenic purpura.

Journal Article J Clin Immunol · September 2008 OBJECTIVE: DNA methylation is known to play an important role in gene transcription and alterations of methylation contribute to the development of certain disorders such as cancer and immunodeficiency. Recent years have found an increasing interest in the ... Full text Link to item Cite

ChemInform Abstract: STAT3: A Critical Transcription Activator in Angiogenesis

Journal Article ChemInform · June 10, 2008 AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, ... Full text Cite

[Expression of recombinant human hemangiopoietin and preparation of its polyclonal antibody].

Journal Article Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi · November 2006 AIM: To express the recombinant fusion protein of hemangiopoietin (HAPO) and prepare the rabbit-anti-human HAPO polyclonal antibody. METHODS: The sequence encoding HAPO was amplified by PCR and cloned into plasmid pET32c to construct recombinant prokaryoti ... Link to item Cite

Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase.

Journal Article J Lipid Res · June 2006 Oxidized low density lipoprotein (OxLDL) is one of the most important risk factors of cardiovascular disease. Here, we study the impact of OxLDL on endothelial progenitor cells (EPCs) and determine whether OxLDL affects EPCs by an inhibitory effect on endo ... Full text Link to item Cite