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Jessica Tyler

Present Title & Affiliation

Primary Appointment

Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

My lab studies the epigenetic regulation of gene expression and genomic integrity. All the activities of the Eukaryotic genome, including DNA repair, gene expression, and DNA replication are tightly regulated by packaging the DNA together with histones into chromatin and by dynamic alterations to this chromatin structure. The goal of our research is to discover novel ways in which the chromatin structure is altered during gene expression and double-strand DNA repair, and to understand how these chromatin dynamics regulate these key nuclear processes. For example, we recently showed for the first time that histones are acetylated and then deacetylated during the process of double-strand DNA repair via homologous recombination, and that failure to do so results in cell death. We have also recently discovered that the removal of histones from promoter regions is essential for transcriptional activation, while the replacement of histones onto promoter regions is essential for transcriptional repression. Our lab is now defining how these and other chromatin changes occur and the molecular mechanisms by which they regulate normal gene expression patterns and double-strand DNA repair. Our studies use a combination of molecular genetic in budding yeast, tissue culture studies, biochemistry, biophysics and structural approaches. The proteins and processes that we study are so highly conserved through eukaryotic evolution, that what we learn in the highly genetically malleable yeast system is directly relevant to the situation in humans. In addition to learning how chromatin regulates fundamental processes in the cell, our studies are helping us to understand how defects in the chromatin structure lead to gene dysfunction and genomic instability, in turn causing human aging and disease states including cancer and leukemia.

Office Address

The University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd.
Unit Number: 1000
Houston, TX 77030
Room Number: BSRB, S9.8336A
Phone: 713-834-6274
Fax: 713-834-6266

Education & Training

Degree-Granting Education

1994 University of Glasgow, Glasgow, Scotland, Doctor of Philosophy in Virology, Virology
1990 University of Sheffield, Sheffield, England, United Kingdom, Bachelor of Science in Biochemistry, First Class Honors, Biochemistry


Academic Appointments

Professor, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4/2010-9/2014

Selected Publications

Peer-Reviewed Original Research Articles

1. Johnson DP, Spitz GS, Tharkar S, Quayle SN, Shearstone JR, Jones S, McDowell ME, Wellman H, Tyler JK, Cairns BR, Chandrasekharan MB, Bhaskara S. HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma. Oncotarget. e-Pub 12/31/2014. PMID: 25605023.
2. Castillo A, Paul A, Sun B, Huang TH, Wang Y, Yazinski SA, Tyler J, Li L, You MJ, Zou L, Yao J, Wang B. The BRCA1-interacting protein, Abraxas, is required for genomic stability and tumor suppression. Cell Rep 8(3):807-17, 8/7/2014. e-Pub 7/24/2014. PMCID: PMC4149256.
3. Das C, Tyler JK, Churchill ME. The histone shuffle: histone chaperones in an energetic dance. Trends Biochem Sci. e-Pub 5/2010. PMID: 20444609.
4. Ransom M, Dennehey BK, Tyler JK. Chaperoning histones during DNA replication and repair. Cell 140(2):183-95, 1/2010. PMID: 20141833.
5. Chen CC, Tyler JK. Selective sensitization of cancer cells to DNA damage by a HAT inhibitor. Cell Cycle 8(18):2867, 9/2009. PMID: 19736512.
6. Ransom M, Williams SK, Dechassa ML, Das C, Linger J, Adkins M, Liu C, Bartholomew B, Tyler JK. FACT and the proteasome promote promoter chromatin disassembly and transcriptional initiation. J Biol Chem 284(35):23461-71, 8/2009. e-Pub 7/2009. PMCID: PMC2749120.
7. Das C, Lucia MS, Hansen KC, Tyler JK. CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459(7243):113-7, 5/2009. e-Pub 3/2009. PMCID: PMC2756583.
8. Ohsawa R, Adkins M, Tyler JK. Epigenetic inheritance of an inducibly nucleosome-depleted promoter and its associated transcriptional state in the apparent absence of transcriptional activators. Epigenetics Chromatin 2(1):11, 2009. PMCID: PMC2749832.
9. Chen CC, Tyler J. Chromatin reassembly signals the end of DNA repair. Cell Cycle 7(24):3792-7, 12/2008. e-Pub 12/2008. PMID: 19066448.
10. Chen CC, Carson JJ, Feser J, Tamburini B, Zabaronick S, Linger J, Tyler JK. Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair. Cell 134(2):231-43, 7/2008. PMCID: PMC2610811.
11. Williams SK, Truong D, Tyler JK. Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation. Proc Natl Acad Sci U S A 105(26):9000-5, 7/2008. e-Pub 6/2008. PMCID: PMC2449354.
12. Adkins MW, Williams SK, Linger J, Tyler JK. Chromatin disassembly from the PHO5 promoter is essential for the recruitment of the general transcription machinery and coactivators. Mol Cell Biol 27(18):6372-82, 9/2007. e-Pub 7/2007. PMCID: PMC2099613.
13. Linger JG, Tyler JK. Chromatin disassembly and reassembly during DNA repair. Mutat Res 618(1-2):52-64, 5/2007. e-Pub 1/2007. PMCID: PMC2593076.
14. Williams SK, Tyler JK. Transcriptional regulation by chromatin disassembly and reassembly. Curr Opin Genet Dev 17(2):88-93, 4/2007. e-Pub 2/2007. PMID: 17307351.
15. Adkins MW, Carson JJ, English CM, Ramey CJ, Tyler JK. The histone chaperone anti-silencing function 1 stimulates the acetylation of newly synthesized histone H3 in S-phase. J Biol Chem 282(2):1334-40, 1/2007. e-Pub 11/2006. PMID: 17107956.
16. English CM, Adkins MW, Carson JJ, Churchill ME, Tyler JK. Structural basis for the histone chaperone activity of Asf1. Cell 127(3):495-508, 11/2006. PMID: 17081973.
17. Linger J, Tyler JK. Global replication-independent histone H4 exchange in budding yeast. Eukaryot Cell 5(10):1780-7, 10/2006. e-Pub 8/2006. PMCID: PMC1595336.
18. Tamburini BA, Carson JJ, Linger JG, Tyler JK. Dominant mutants of the Saccharomyces cerevisiae ASF1 histone chaperone bypass the need for CAF-1 in transcriptional silencing by altering histone and Sir protein recruitment. Genetics 173(2):599-610, 6/2006. e-Pub 4/2006. PMCID: PMC1526541.
19. Schulz LL, Tyler JK. The histone chaperone ASF1 localizes to active DNA replication forks to mediate efficient DNA replication. FASEB J 20(3):488-90, 3/2006. e-Pub 1/2006. PMID: 16396992.
20. Adkins MW, Tyler JK. Transcriptional activators are dispensable for transcription in the absence of Spt6-mediated chromatin reassembly of promoter regions. Mol Cell 21(3):405-16, 2/2006. PMID: 16455495.
21. Linger J, Tyler JK. The yeast histone chaperone chromatin assembly factor 1 protects against double-strand DNA-damaging agents. Genetics 171(4):1513-22, 12/2005. e-Pub 9/2005. PMCID: PMC1456080.
22. English CM, Maluf NK, Tripet B, Churchill ME, Tyler JK. ASF1 binds to a heterodimer of histones H3 and H4: a two-step mechanism for the assembly of the H3-H4 heterotetramer on DNA. Biochemistry 44(42):13673-82, 10/2005. PMID: 16229457.
23. Tamburini BA, Carson JJ, Adkins MW, Tyler JK. Functional conservation and specialization among eukaryotic anti-silencing function 1 histone chaperones. Eukaryot Cell 4(9):1583-90, 9/2005. PMCID: PMC1214205.
24. Tamburini BA, Tyler JK. Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair. Mol Cell Biol 25(12):4903-13, 6/2005. PMCID: PMC1140608.
25. Zabaronick SR, Tyler JK. The histone chaperone anti-silencing function 1 is a global regulator of transcription independent of passage through S phase. Mol Cell Biol 25(2):652-60, 1/2005. PMCID: PMC543432.
26. Schulz L, & Tyler JK. Heterochromatin focuses on senescence. Molecular Cell 17:168-170, 2005.
27. Ramey CJ, Howar S, Adkins M, Linger J, Spicer J, Tyler JK. Activation of the DNA damage checkpoint in yeast lacking the histone chaperone anti-silencing function 1. Mol Cell Biol 24(23):10313-27, 12/2004. PMCID: PMC529054.
28. Adkins MW, Tyler JK. The histone chaperone Asf1p mediates global chromatin disassembly in vivo. J Biol Chem 279(50):52069-74, 12/2004. e-Pub 9/2004. PMID: 15452122.
29. Adkins MW, Howar SR, Tyler JK. Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes. Mol Cell 14(5):657-66, 6/2004. PMID: 15175160.
30. Tyler JK. Chromatin assembly. Cooperation between histone chaperones and ATP-dependent nucleosome remodeling machines. Eur J Biochem 269(9):2268-74, 5/2002. PMID: 11985607.
31. Tyler JK, Collins KA, Prasad-Sinha J, Amiott E, Bulger M, Harte PJ, Kobayashi R, Kadonaga JT. Interaction between the Drosophila CAF-1 and ASF1 chromatin assembly factors. Mol Cell Biol 21(19):6574-84, 10/2001. PMCID: PMC99803.
32. Tyler JK, Adams CR, Chen SR, Kobayashi R, Kamakaka RT, Kadonaga JT. The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature 402(6761):555-60, 12/1999. PMID: 10591219.
33. Tyler JK, Kadonaga JT. The "dark side" of chromatin remodeling: repressive effects on transcription. Cell 99(5):443-6, 11/1999. PMID: 10589670.
34. Ito T, Tyler JK, Kadonaga JT. Chromatin assembly factors: a dual function in nucleosome formation and mobilization? Genes Cells 2(10):593-600, 10/1997. PMID: 9427281.
35. Tyler JK, Orr A, Everett RD. Replacement of the herpes simplex virus type 1 Vmw175 DNA binding domain with its varicella-zoster virus counterpart results in a protein with novel regulatory properties that can support virus growth. J Gen Virol 78 ( Pt 1):179-88, 1/1997. PMID: 9010302.
36. Tyler JK, Bulger M, Kamakaka RT, Kobayashi R, Kadonaga JT. The p55 subunit of Drosophila chromatin assembly factor 1 is homologous to a histone deacetylase-associated protein. Mol Cell Biol 16(11):6149-59, 11/1996. PMCID: PMC231618.
37. Ito T, Tyler JK, Bulger M, Kobayashi R, Kadonaga JT. ATP-facilitated chromatin assembly with a nucleoplasmin-like protein from Drosophila melanogaster. J Biol Chem 271(40):25041-8, 10/1996. PMID: 8798787.
38. Tyler JK, Everett RD. The DNA binding domains of the varicella-zoster virus gene 62 and herpes simplex virus type 1 ICP4 transactivator proteins heterodimerize and bind to DNA. Nucleic Acids Res 22(5):711-21, 3/1994. PMCID: PMC307873.
39. Tyler JK, Allen KE, Everett RD. Mutation of a single lysine residue severely impairs the DNA recognition and regulatory functions of the VZV gene 62 transactivator protein. Nucleic Acids Res 22(3):270-8, 2/1994. PMCID: PMC523576.
40. Tyler JK, Everett RD. The DNA binding domain of the varicella-zoster virus gene 62 protein interacts with multiple sequences which are similar to the binding site of the related protein of herpes simplex virus type 1. Nucleic Acids Res 21(3):513-22, 2/1993. PMCID: PMC309147.
41. Everett R, Cross A, Tyler J, and Orr A. An epitope within the DNA-binding domain of therherpes simplex virus immediate early protein Vmw175 is conserved in the Varicella-zoster virus gene 62 protein. The Journal of General Virology 74:1955-1958, 1993.

Last updated: 3/31/2015