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Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Fibrosis-The Tale Of H3k27 Histone Methyltransferases And Demethylases, Morgan D. Basta, Svetlana Petruk, Alexander Mazo, Janice L. Walker
Fibrosis-The Tale Of H3k27 Histone Methyltransferases And Demethylases, Morgan D. Basta, Svetlana Petruk, Alexander Mazo, Janice L. Walker
Department of Biochemistry and Molecular Biology Faculty Papers
Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 …
Cbf-1 Promotes The Establishment And Maintenance Of Hiv Latency By Recruiting Polycomb Repressive Complexes, Prc1 And Prc2, At Hiv Ltr., Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Shilpa Sonti, Sonia Zicari, Lin Sun, Aseel Alqatawni, Michael Bukrinsky, Gary Simon, Ashok Chauhan, René Daniel, Mudit Tyagi
Cbf-1 Promotes The Establishment And Maintenance Of Hiv Latency By Recruiting Polycomb Repressive Complexes, Prc1 And Prc2, At Hiv Ltr., Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Shilpa Sonti, Sonia Zicari, Lin Sun, Aseel Alqatawni, Michael Bukrinsky, Gary Simon, Ashok Chauhan, René Daniel, Mudit Tyagi
Center for Translational Medicine Faculty Papers
The C-promoter binding factor-1 (CBF-1) is a potent and specific inhibitor of the human immunodeficiency virus (HIV)-1 LTR promoter. Here, we demonstrate that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. Chromatin immunoprecipitation (ChIP) assays using latently infected primary T cells and Jurkat T-cell lines demonstrated that CBF-1 induces the establishment and maintenance of HIV latency by recruiting polycomb group (PcG/PRC) corepressor complexes or polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Knockdown of CBF-1 resulted in the dissociation of PRCs …
Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey
Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey
Department of Cancer Biology Faculty Papers
The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …
Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations In Prostate Cancer., Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills
Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations In Prostate Cancer., Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills
Kimmel Cancer Center Papers, Presentations, and Grand Rounds
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene …
Chromatin To Clinic: The Molecular Rationale For Parp1 Inhibitor Function., Felix Y. Feng, Johann S. De Bono, Mark A. Rubin, Karen E Knudsen
Chromatin To Clinic: The Molecular Rationale For Parp1 Inhibitor Function., Felix Y. Feng, Johann S. De Bono, Mark A. Rubin, Karen E Knudsen
Department of Cancer Biology Faculty Papers
Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.
Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell
Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell
Department of Cancer Biology Faculty Papers
The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …
Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught
Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught
Department of Biochemistry and Molecular Biology Faculty Papers
Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich …
Transcriptional Regulation Network Analysis Of The Hypertension-Perturbed Nucleus Tractus Solitarius, Gregory E. Gonye, Rajanikanth Vadigepalli, Haiping Hao, James S. Schwaber
Transcriptional Regulation Network Analysis Of The Hypertension-Perturbed Nucleus Tractus Solitarius, Gregory E. Gonye, Rajanikanth Vadigepalli, Haiping Hao, James S. Schwaber
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Poster Presentation.
Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell
Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The position effect variegation in Drosophila and Schizosaccharomyces pombe, and higher-order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group, (e.g., histone deacetylases ([HDACs]), protein phosphatases) and enhancer E(Var) group (e.g., ATP [adenosine 5'-triphosphate]-dependent nucleosome remodeling proteins). Higher-order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin, and histone tails in turn serve as platforms for recruitment of signaling modules that include nonhistone proteins such as heterochromatin protein (HP1) and NuRD. Because the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also …
All-1/Mll1, A Homologue Of Drosophila Trithorax, Modifies Chromatin And Is Directly Involved In Infant Acute Leukaemia., E Canaani, T Nakamura, T Rozovskaia, S T Smith, T Mori, C M Croce, Alexander Mazo
All-1/Mll1, A Homologue Of Drosophila Trithorax, Modifies Chromatin And Is Directly Involved In Infant Acute Leukaemia., E Canaani, T Nakamura, T Rozovskaia, S T Smith, T Mori, C M Croce, Alexander Mazo
Kimmel Cancer Center Faculty Papers
Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of >50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX.