title: SMCX and components of the TIP60 complex contribute to E2 regulation of the HPV E6/E7 promoter.
abstract: An important step in the malignant progression of HPV-associated lesions is the dysregulation of expression of the viral E6 and E7 oncogenes. This is often achieved through the loss of expression of E2, which represses the HPV LCR promoter and E6/E7 expression. Our previous studies confirmed a role for Brd4 in mediating the E2 transcriptional repression function, and identified JARID1C/SMCX and EP400 as contributors to E2-mediated repression. Here we show that TIP60, a component of the TIP60/TRRAP histone acetyltransferase complex, also contributes to the E2 repression function, and we extend our studies on SMCX. Di- and tri-methyl marks on histone H3K4 are reduced in the presence of E2 and SMCX, suggesting a mechanism by which SMCX contributes to E2-mediated repression of the HPV LCR. Together, these findings lead us to hypothesize that E2 recruits histone-modifying cellular proteins to the HPV LCR, resulting in transcriptional repression of E6 and E7.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Friederike S
authors.initials: FS
authors.lastname: Haberstroh
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: White
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, United States; Department of Medicine, Brigham and Women׳s Hospital, Boston, MA 02115 and Harvard Medical School, Boston, MA 02115, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Livingston
authors.affiliation: Department of Medicine, Brigham and Women׳s Hospital, Boston, MA 02115 and Harvard Medical School, Boston, MA 02115, United States; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, United States. Electronic address: peter_howley@hms.harvard.edu.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Howley
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D056466:Histone Demethylases; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D056466:Histone Demethylases; D000074443:Lysine Acetyltransferase 5; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D010089:Oxidoreductases, N-Demethylating; D021122:Protein Subunits; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C054855:E2 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; C086877:KDM5C protein, human; C098489:KAT5 protein, human; C498558:EP400 protein, human
keywords: Chromatin; E2; EP400; H3K4; LCR; Methylation; Papillomavirus; SMCX; TIP60; Transcriptional repression