A new paradigm for transcription factor TFIIB functionality.
Experimental and bioinformatic studies of transcription initiation by RNA polymerase II (RNAP2) have revealed a mechanism of RNAP2 transcription initiation less uniform across gene promoters than initially thought. However, the general transcription factor TFIIB is presumed to be universally required for RNAP2 transcription initiation. Based on bioinformatic analysis of data and effects of TFIIB knockdown in primary and transformed cell lines on cellular functionality and global gene expression, we report that TFIIB is dispensable for transcription of many human promoters, but is essential for herpes simplex virus-1 (HSV-1) gene transcription and replication. We report a novel cell cycle TFIIB regulation and localization of the acetylated TFIIB variant on the transcriptionally silent mitotic chromatids. Taken together, these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects.
1] Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA [2].
Vladimir
V
Gelev
1] Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA [2].
Janice M
JM
Zabolotny
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Martin
M
Lange
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Makoto
M
Hiromura
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Sang Wook
SW
Yoo
Department of Microbiology and Molecular Genetics, Program in Virology, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Joseph S
JS
Orlando
Department of Microbiology and Molecular Genetics, Program in Virology, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Anna
A
Kushnir
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Nobuo
N
Horikoshi
Centre Hospitalier Universitaire de Québec (CHUQ)-Centre de Recherche, Hopital L'Hôtel-Dieu de Québec et Université Laval, Québec G1R 2J6, Canada.
Eric
E
Paquet
Centre Hospitalier Universitaire de Québec (CHUQ)-Centre de Recherche, Hopital L'Hôtel-Dieu de Québec et Université Laval, Québec G1R 2J6, Canada.
Dimcho
D
Bachvarov
Department of Microbiology and Molecular Genetics, Program in Virology, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Priscilla A
PA
Schaffer
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Anny
A
Usheva
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D066264:Datasets as Topic; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005804:Genes, Lethal; D015894:Genome, Human; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D059467:Transcriptome
D035581:Transcription Factor TFIIB; D012319:RNA Polymerase II