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Department of Biochemistry and Molecular Biology Faculty Papers

2021

Thomas Jefferson University

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An Insulator Blocks Access To Enhancers By An Illegitimate Promoter, Preventing Repression By Transcriptional Interference., Miki Fujioka, Anastasiya Nezdyur, James B. Jaynes Apr 2021

An Insulator Blocks Access To Enhancers By An Illegitimate Promoter, Preventing Repression By Transcriptional Interference., Miki Fujioka, Anastasiya Nezdyur, James B. Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Several distinct activities and functions have been described for chromatin insulators, which separate genes along chromosomes into functional units. Here, we describe a novel mechanism of functional separation whereby an insulator prevents gene repression. When the homie insulator is deleted from the end of a Drosophila even skipped (eve) locus, a flanking P-element promoter is activated in a partial eve pattern, causing expression driven by enhancers in the 3' region to be repressed. The mechanism involves transcriptional read-through from the flanking promoter. This conclusion is based on the following. Read-through driven by a heterologous enhancer is sufficient to repress, even …


Three-Dimensional Structure Of Human Cyclooxygenase (Hcox)-1., Morena Miciaccia, Benny Danilo Belviso, Mariaclara Iaselli, Gino Cingolani, Savina Ferorelli, Marianna Cappellari, Paola Loguercio Polosa, Maria Grazia Perrone, Rocco Caliandro, Antonio Scilimati Feb 2021

Three-Dimensional Structure Of Human Cyclooxygenase (Hcox)-1., Morena Miciaccia, Benny Danilo Belviso, Mariaclara Iaselli, Gino Cingolani, Savina Ferorelli, Marianna Cappellari, Paola Loguercio Polosa, Maria Grazia Perrone, Rocco Caliandro, Antonio Scilimati

Department of Biochemistry and Molecular Biology Faculty Papers

The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined …