Boyer 359

Arnie Berk is a virologist and cell biologist in the Molecular Biology Institute and Department of Microbiology, Immunology and Molecular Genetics at UCLA. As a postdoctoral fellow, his analysis of adenovirus mRNA synthesis led to the initial discovery of RNA processing of spliced mRNAs from pre-mRNA precursors containing introns, and his analysis of early SV40 mRNA lead to the initial discovery of alternatively spliced mRNA isoforms encoding distinct, but related proteins. At UCLA his research has focused on the mechanisms of transcriptional activation and control of the cell cycle by the adenovirus E1A and E1B proteins. Work from his laboratory demonstrated that the tumor suppressor activity of p53 depends on its activity as a transcriptional activator. His laboratory discovered that activation of transcription by the adenovirus large E1A protein results from its interaction with the human mediator of transcription complex, and that this promotes assembly of pre-initiation complexes on promoter DNA and stimulation of elongation by promoter proximal paused RNA polymerase II. The small E1A protein was shown to regulate host cell transcription and cell cycle progression through modifications of chromatin structure. He is a Fellow of the American Academy of Arts and Sciences and holds the UCLA Presidential Chair in Molecular Cell Biology.

We study molecular interactions that regulate transcription and the cell cycle in mammalian cells, focusing particular attention on transcription factors encoded by oncogenes and tumor suppressors. Since the decision to initiate transcription is the key control point regulating expression of most genes, transcriptional regulation determines the properties of both normal and abnormal cells. Many of our projects involve proteins expressed early during infection by DNA viruses because these proteins have evolved to interact with key host cell regulatory proteins in order to maximize the yield of progeny virions. Consequently, they have directed us to critical cellular regulatory proteins with which they interact, such as p53, the Retinoblastoma protein family, the mediator of transcription complex, and chromatin modifying complexes.

Ferrari Roberto, Gou Dawei, Jawdekar Gauri, Johnson Sarah A, Nava Miguel, Su Trent, Yousef Ahmed F, Zemke Nathan R, Pellegrini Matteo, Kurdistani Siavash K, Berk Arnold J Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection. Cell host & microbe. 2014; 16(5): 663-76.

Gallaher Sean D, Berk Arnold J A rapid Q-PCR titration protocol for adenovirus and helper-dependent adenovirus vectors that produces biologically relevant results. Journal of virological methods. 2013; 192(1-2): 28-38.

Berk Arnold J Yin and yang of mediator function revealed by human mutants. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(48): 19519-20.

Ferrari Roberto, Su Trent, Li Bing, Bonora Giancarlo, Oberai Amit, Chan Yvonne, Sasidharan Rajkumar, Berk Arnold J, Pellegrini Matteo, Kurdistani Siavash K Reorganization of the host epigenome by a viral oncogene. Genome research. 2012; 22(7): 1212-21.

Kawamata N, Pennella M A, Woo J L, Berk A J, Koeffler H P Dominant-negative mechanism of leukemogenic PAX5 fusions. Oncogene. 2012; 31(8): 966-77.

Pennella Mario A, Liu Yue, Woo Jennifer L, Kim Chongwoo A, Berk Arnold J Adenovirus E1B 55-kilodalton protein is a p53-SUMO1 E3 ligase that represses p53 and stimulates its nuclear export through interactions with promyelocytic leukemia nuclear bodies. Journal of virology. 2010; 84(23): 12210-25.

Gil J S, Gallaher S D, Berk A J Delivery of an EBV episome by a self-circularizing helper-dependent adenovirus: long-term transgene expression in immunocompetent mice. Gene therapy. 2010; 17(10): 1288-93.

Balamotis Michael A, Pennella Mario A, Stevens Jennitte L, Wasylyk Bohdan, Belmont Andrew S, Berk Arnold J Complexity in transcription control at the activation domain-mediator interface. Science signaling. 2009; 2(69): ra20.

Ferrari Roberto, Berk Arnold J, Kurdistani Siavash K Viral manipulation of the host epigenome for oncogenic transformation. Nature reviews. Genetics. 2009; 10(5): 290-4.

Horwitz Gregory A, Zhang Kangling, McBrian Matthew A, Grunstein Michael, Kurdistani Siavash K, Berk Arnold J Adenovirus small e1a alters global patterns of histone modification. Science (New York, N.Y.). 2008; 321(5892): 1084-5.

Ferrari Roberto, Pellegrini Matteo, Horwitz Gregory A, Xie Wei, Berk Arnold J, Kurdistani Siavash K Epigenetic reprogramming by adenovirus e1a. Science (New York, N.Y.). 2008; 321(5892): 1086-8.

Woo Jennifer L, Berk Arnold J Adenovirus ubiquitin-protein ligase stimulates viral late mRNA nuclear export. Journal of virology. 2007; 81(2): 575-87.

Liu Yue, Shevchenko Anna, Shevchenko Andrej, Berk Arnold J Adenovirus exploits the cellular aggresome response to accelerate inactivation of the MRN complex. Journal of virology. 2005; 79(22): 14004-16.

Berk Arnold J Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Oncogene. 2005; 24(52): 7673-85.

Wang Gang, Balamotis Michael A, Stevens Jennitte L, Yamaguchi Yuki, Handa Hiroshi, Berk Arnold J Mediator requirement for both recruitment and postrecruitment steps in transcription initiation. Molecular cell. 2005; 17(5): 683-94.

Bourbon Henri-Marc, Aguilera Andres, Ansari Aseem Z, Asturias Francisco J, Berk Arnold J, Bjorklund Stefan, Blackwell T Keith, Borggrefe Tilman, Carey Michael, Carlson Marian, Conaway Joan W, Conaway Ronald C, Emmons Scott W, Fondell Joseph D, Freedman Leonard P, Fukasawa Toshio, Gustafsson Claes M, Han Min, He Xi, Herman Paul K, Hinnebusch Alan G, Holmberg Steen, Holstege Frank C, Jaehning Judith A, Kim Young-Joon, Kuras Laurent, Leutz Achim, Lis John T, Meisterernest Michael, Naar Anders M, Nasmyth Kim, Parvin Jeffrey D, Ptashne Mark, Reinberg Danny, Ronne Hans, Sadowski Ivan, Sakurai Hiroshi, Sipiczki Matthias, Sternberg Paul W, Stillman David J, Strich Randy, Struhl Kevin, Svejstrup Jasper Q, Tuck Simon, Winston Fred, Roeder Robert G, Kornberg Roger D A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II.Molecular cell. 2004; 14(5): 553-7.

Cantin Greg T, Stevens Jennitte L, Berk Arnold J Activation domain-mediator interactions promote transcription preinitiation complex assembly on promoter DNA. Proceedings of the National Academy of Sciences of the United States of America. 2003; 100(21): 12003-8.

Harada Josephine N, Shevchenko Anna, Shevchenko Andrej, Pallas David C, Berk Arnold J Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery. Journal of virology. 2002; 76(18): 9194-206.

Wang Gang, Berk Arnold J In vivo association of adenovirus large E1A protein with the human mediator complex in adenovirus-infected and -transformed cells. Journal of virology. 2002; 76(18): 9186-93.

Martel Lisa S, Brown Helen J, Berk Arnold J Evidence that TAF-TATA box-binding protein interactions are required for activated transcription in mammalian cells. Molecular and cellular biology. 2002; 22(8): 2788-98.

Stevens Jennitte L, Cantin Greg T, Wang Gang, Shevchenko Andrej, Shevchenko Anna, Berk Arnold J Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit. Science (New York, N.Y.). 2002; 296(5568): 755-8.

Berk A J TBP-like factors come into focus. Cell. 2000; 103(1): 5-8.

Boyer T G, Martin M E, Lees E, Ricciardi R P, Berk A J Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature. 1999; 399(6733): 276-9.

Kobayashi N, Horn P J, Sullivan S M, Triezenberg S J, Boyer T G, Berk A J DA-complex assembly activity required for VP16C transcriptional activation.Molecular and cellular biology. 1998; 18(7): 4023-31.

Shen Y, Kassavetis G A, Bryant G O, Berk A J Polymerase (Pol) III TATA box-binding protein (TBP)-associated factor Brf binds to a surface on TBP also required for activated Pol II transcription. Molecular and cellular biology. 1998; 18(3): 1692-700.

Bryant G O, Martel L S, Burley S K, Berk A J Radical mutations reveal TATA-box binding protein surfaces required for activated transcription in vivo. Genes & development. 1996; 10(19): 2491-504.

Juo Z S, Chiu T K, Leiberman P M, Baikalov I, Berk A J, Dickerson R E How proteins recognize the TATA box. Journal of molecular biology. 1996; 261(2): 239-54.

Berk A J Biochemistry meets genetics in the holoenzyme. Proceedings of the National Academy of Sciences of the United States of America. 1995; 92(26): 11952-4.

Martinez E, Zhou Q, L’Etoile N D, Oelgeschläger T, Berk A J, Roeder R G Core promoter-specific function of a mutant transcription factor TFIID defective in TATA-box binding. Proceedings of the National Academy of Sciences of the United States of America. 1995; 92(25): 11864-8.

Kobayashi N, Boyer T G, Berk A J A class of activation domains interacts directly with TFIIA and stimulates TFIIA-TFIID-promoter complex assembly.Molecular and cellular biology. 1995; 15(11): 6465-73.

Lieberman P M, Berk A J A mechanism for TAFs in transcriptional activation: activation domain enhancement of TFIID-TFIIA–promoter DNA complex formation. Genes & development. 1994; 8(9): 995-1006.

L’Etoile N D, Fahnestock M L, Shen Y, Aebersold R, Berk A J Human transcription factor IIIC box B binding subunit. Proceedings of the National Academy of Sciences of the United States of America. 1994; 91(5): 1652-6.

Zhou Q, Lieberman P M, Boyer T G, Berk A J Holo-TFIID supports transcriptional stimulation by diverse activators and from a TATA-less promoter. Genes & development. 1992; 6(10): 1964-74.

Yew P R, Berk A J Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature. 1992; 357(6373): 82-5.

Kao C C, Lieberman P M, Schmidt M C, Zhou Q, Pei R, Berk A J Cloning of a transcriptionally active human TATA binding factor. Science (New York, N.Y.). 1990; 248(4963): 1646-50.

Schmidt M C, Kao C C, Pei R, Berk A J Yeast TATA-box transcription factor gene. Proceedings of the National Academy of Sciences of the United States of America. 1989; 86(20): 7785-9.

Berk AJ, Sharp PA. Spliced early messenger RNAs of simian virus 40. Proc. Natl. Acad. Sci. USA 1978; 75: 1274-1278.

Berget SM, Berk AJ, Harrison T, Sharp PA Spliced segments at the 5′ termini of adenovirus 2 late mRNA: a role for heterogeneous nuclear RNA in mammalian cells. Cold Spring Harbor Symposium on Quantitative Biology 1978; 42: 523-529.

Berk AJ, Sharp PA Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of Sl endonuclease-digested hybrids. Cell 1977; 12: 721-732.