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Michelle C. Barton, Ph.D.

Present Title & Affiliation

Primary Appointment

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

Research Interests

Chromatin, transcription, p53 tumor suppressor, stem cells

 

Our laboratory is focused on basic mechanisms of regulated and aberrant gene expression during development, tissue regeneration and cancer, especially as dictated by members of the p53-super family and their interacting protein partners.  We are using a combination of in vitro biochemical approaches and mouse models to define transcription regulation by p53 in terms of chromatin structure and function.  Recently we developed embryonic stem cell lines and mice that express endogenous p53 protein that is epitope-tagged.  We identified TRIM24 as a previously unknown E3-ubiquitin ligase of p53, and showed that it establishes an auto-regulatory loop of p53-regulation.  Further, this work led us to uncover the role of TRIM24 in breast cancer, where it is aberrantly over expressed and activates estrogen signaling.  With our model systems, we are determining how TRIM24 negatively impacts breast cancer, how p53 is regulated in stem cells, the roles of p53 in differentiation, and how p53-mediated regulation is disrupted during liver regeneration and hepatocellular carcinogenesis.


Laboratory webpage:


http://www.mdanderson.org/education-and-research/departments-programs-and-labs/labs/barton-laboratory/index.html


 

Office Address

The University of Texas MD Anderson Cancer Center
6767 Bertner St.
Unit Number: 1000
Houston, TX 77030
Room Number: S9.8116B
Phone: 713-834-6268
Fax: 713-834-6273

Education & Training

Degree-Granting Education

1989 University of Illinois, Urbana, IL, PHD, Biochemistry
1978 University of Illinois, Urbana, IL, BS, Biochemistry

Postgraduate Training

9/1989-10/1994 Research Fellowship, Chromatin regulation, The Salk Institute for Biological Studies, La Jolla, CA, Beverly Emerson

Experience/Service

Academic Appointments

Professor, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 9/2008-9/2014

Administrative Appointments/Responsibilities

Co-Director, Center for Stem Cell and Developmental Biology, The University of Texas MD Anderson Cancer Center, Center for Stem Cell and Developmental Biology, Houston, TX, 12/2009-present

Honors and Awards

2012 Paul Darlington Award for Outstanding Mentoring, GSBS
2011-2016 Ashbel Smith Endowed Professor, University of Texas
2009 Robert M. Chamberlain, Distinguished Mentor Award, Postdoctoral Association of M.D. Anderson Cancer Center
2008 M. D. Anderson Cancer Center Faculty Achievement Award in Education, U. T. M. D. Anderson Cancer Center

Selected Publications

Peer-Reviewed Original Research Articles

1. Coban Z, Barton MC. Integrative genomics: Liver regeneration and hepatocellular carcinoma. J Cell Biochem 113(7):2179-84, 7/2012. e-Pub 2/17/2012. PMCID: PMC3350570.
2. Bochkis IM, Schug J, Ye DZ, Kurinna S, Stratton SA, Barton MC, Kaestner KH. Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators foxa1 and foxa2. PLoS Genet 8(6):e1002770, 2012. e-Pub 6/21/2012. PMCID: PMC3380847.
3. Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, Kyba M, Barton MC. p53 Regulates Cell Cycle and MicroRNAs to Promote Differentiation of Human Embryonic Stem Cells. PLoS Biol 10(2):e1001268, 2012. e-Pub 2/28/2012. PMCID: PMC3289600.
4. Wilson MA, Koutelou E, Hirsch C, Akdemir K, Schibler A, Barton MC, Dent SY. Ubp8 and SAGA regulate Snf1 AMP kinase activity. Mol Cell Biol 31(15):3126-35, 8/2011. e-Pub 5/31/2011. PMCID: PMC3147604.
5. Mao CA, Tsai WW, Cho JH, Pan P, Barton MC, Klein WH. Neuronal transcriptional repressor REST suppresses an Atoh7-independent program for initiating retinal ganglion cell development. Dev Biol 349(1):90-9, 1/1/2011. e-Pub 10/20/2010. PMCID: PMC2993882.
6. Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC. TRIM24 links a non-canonical histone signature to breast cancer. Nature 468(7326):927-32, 12/16/2010. PMID: 21164480.
7. Dejosez M, Levine SS, Frampton GM, Whyte WA, Stratton SA, Barton MC, Gunaratne PH, Young RA, Zwaka TP. Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev 24(14):1479-84, 7/15/2010. e-Pub 6/25/2010. PMCID: PMC2904937.
8. Kurinna S, Stratton SA, Tsai WW, Akdemir KC, Gu W, Singh P, Goode T, Darlington GJ, Barton MC. Direct activation of forkhead box O3 by tumor suppressors p53 and p73 is disrupted during liver regeneration in mice. Hepatology. e-Pub 6/16/2010. PMID: 20564353.
9. Taube JH, Allton K, Duncan SA, Shen L, Barton MC. Foxa1 functions as a pioneer transcription factor at transposable elements to activate Afp during differentiation of embryonic stem cells. J Biol Chem 285(21):16135-44, 5/21/2010. e-Pub 3/26/2010. PMCID: PMC2871482.
10. Allton K, Jain A, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton M. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A 106(28):11612-6, 7/14/2009. e-Pub 6/25/2009. PMCID: PMC2710642.
11. Johnson AB, Denko N, Barton MC. Hypoxia induces a novel signature of chromatin modifications and global repression of transcription. Mutat Res 640(1-2):174-9, 4/2008. e-Pub 1/2008. PMCID: PMC2346607.
12. Wilkinson DS, Tsai WW, Schumacher MA, Barton MC. Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. Mol Cell Biol 28(6). e-Pub 1/2008. PMCID: PMC2268392.
13. Tsai WW, Nguyen TT, Shi Y, Barton MC. p53-targeted LSD1 functions in repression of chromatin structure and transcription in vivo. Mol Cell Biol 28(17):5139-5146, 2008. e-Pub 6/23/2008. PMCID: PMC2519740.
14. Xie Z, Zhang H, Tsai W, Zhang Y, Du Y, Zhong J, Szpirer C, Zhu M, Cao X, Barton MC, Grusby MJ, Zhang WJ.. Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver. Proc Natl Acad Sci U S A 105(31):10859-10864, 2008. e-Pub 7/31/2008. PMCID: PMC2504784.
15. Qian J, Steigerwald K, Combs KA, Barton MC, Groden J. Caspase cleavage of the APC tumor suppressor and release of an amino-terminal domain is required for the transcription-independent function of APC in apoptosis. Oncogene 26(33):4872-6, 7/2007. e-Pub 2/2007. PMID: 17297457.
16. Chen L, Firozi P, Barton M, Templeton NS. Widespread, exceptionally high levels of histone H3 lysine-4 tri-methylation largely mediate "privileged" gene expression. Gene Expression 13:271-282, 2007.
17. Cui R, Nguyen TT, Taube JH, Stratton SA, Feuerman MH, Barton MC. Family members p53 and p73 act together in chromatin modification and direct repression of alpha-fetoprotein transcription. J Biol Chem 280(47):39152-60, 11/2005. e-Pub 10/2/2005. PMID: 16203738.
18. Park JI, Kim SW, Lyons JP, Ji H, Nguyen TT, Cho K, Barton MC, Deroo T, Vleminckx K, Moon RT, McCrea PD. Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. Dev Cell 8(6):843-54, 6/2005. PMID: 15935774.
19. Nguyen TT, Cho K, Stratton SA, Barton MC. Transcription factor interactions and chromatin modifications associated with p53-mediated, developmental repression of the alpha-fetoprotein gene. Mol Cell Biol 25(6):2147-57, 3/2005. PMCID: PMC1061614.
20. Wilkinson DS, Ogden SK, Stratton SA, Piechan JL, Nguyen TT, Smulian GA, Barton MC. A direct intersection between p53 and transforming growth factor beta pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene. Mol Cell Biol 25(3):1200-12, 2/2005. PMCID: PMC544019.
21. Steigerwald K, Behbehani GK, Combs KA, Barton MC, Groden J. The APC tumor suppressor promotes transcription-independent apoptosis in vitro. Mol Cancer Res 3(2):78-89, 2/2005. PMID: 15755874.
22. Denko N, Wernke-Dollries K, Johnson AB, Hammond E, Chiang CM, Barton MC. Hypoxia actively represses transcription by inducing negative cofactor 2 (Dr1/DrAP1) and blocking preinitiation complex assembly. J Biol Chem 278:5744-9, 2/2003. PMID: 12477712.
23. Ogden SK, Lee KC, Wernke-Dollries K, Stratton SA, Aronow B, Barton MC. p53 targets chromatin structure alteration to repress alpha-fetoprotein gene expression. J Biol Chem 276:42057-62, 11/2001. PMID: 11572852.
24. Ogden SK, Lee KC, Barton MC. Hepatitis B viral transactivator HBx alleviates p53-mediated repression of alpha-fetoprotein gene expression. J Biol Chem 275:27806-14, 9/2000. PMID: 10842185.
25. Rockx DA, Mason R, van Hoffen A, Barton MC, Citterio E, Bregman DB, van Zeeland AA, Vrieling H, Mullenders LH. UV-induced inhibition of transcription involves repression of transcription initiation and phosphorylation of RNA polymerase II. Proc Natl Acad Sci U S A 97:10503-8, 9/2000. PMID: 10973477.
26. Crowe AJ, Piechan JL, Sang L, Barton MC. S-Phase progression mediates activation of a silenced gene in synthetic nuclei. Mol Cell Biol 20:4169-80, 6/2000. PMID: 10805758.
27. Kroll SL, Paulding WR, Schnell PO, Barton MC, Conaway JW, Conaway RC, Czyzyk-Krzeska MF. von Hippel-Lindau protein induces hypoxia-regulated arrest of tyrosine hydroxylase transcript elongation in pheochromocytoma cells. J Biol Chem 274:30109-14, 10/1999. PMID: 10514498.
28. Crowe AJ, Sang L, Li KK, Lee KC, Spear BT, Barton MC. Hepatocyte nuclear factor 3 relieves chromatin-mediated repression of the alpha-fetoprotein gene. J Biol Chem 274:25113-20, 8/1999. PMID: 10455192.
29. Lee KC, Crowe AJ, Barton MC. p53-mediated repression of alpha-fetoprotein gene expression by specific DNA binding. Mol Cell Biol 19:1279-88, 2/1999. PMID: 9891062.
30. Crowe AJ, Barton MC. In vitro reconstitution of nuclei for replication and transcription. Methods Enzymol 304:63-76, 1999. PMID: 10372356.
31. Barton MC, Madani N, Emerson BM. Distal enhancer regulation by promoter derepression in topologically constrained DNA in vitro. Proc Natl Acad Sci U S A 94:7257-62, 7/1997. PMID: 9207078.
32. Denko N, Langland R, Barton M, Lieberman MA. Uncoupling of S-phase and mitosis by recombinant cytotoxic necrotizing factor 2 (CNF2). Exp Cell Res 234:132-8, 7/1997. PMID: 9223378.
33. Barton MC, Emerson BM. Regulated gene expression in reconstituted chromatin and synthetic nuclei. Methods Enzymol 274:299-312, 1996. PMID: 8902814.
34. Barton MC, Emerson BM. Regulated expression of the beta-globin gene locus in synthetic nuclei. Genes Dev 8:2453-65, 10/1994. PMID: 7958909.
35. Barton MC, Hoekstra MF, Emerson BM. Site-directed, recombination-mediated mutagenesis of a complex gene locus. Nucleic Acids Res 18:7349-55, 12/1990. PMID: 2175433.
36. Barton MC, Shapiro DJ. Transient administration of estradiol-17 beta establishes an autoregulatory loop permanently inducing estrogen receptor mRNA. Proc Natl Acad Sci U S A 85:7119-23, 10/1988. PMID: 3174624.
37. McKearin DM, Barton MC, Keller MJ, Shapiro DJ. Estrogen induces transcription of the Xenopus laevis serum retinol-binding protein gene. J Biol Chem 262:4939-42, 4/1987. PMID: 3558378.
38. Keller GA, Barton MC, Shapiro DJ, Singer SJ. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase is present in peroxisomes in normal rat liver cells. Proc Natl Acad Sci U S A 82:770-4, 2/1985. PMID: 3883347.
39. Hayward MA, Barton MC, Shapiro DJ. Coordinate estrogen induction of vitellogenin and a small serum protein mRNA in Xenopus laevis liver. Mol Cell Endocrinol 39:91-8, 2/1985. PMID: 3838520.
40. Clark RE, Martin GG, Barton MC, Shapiro DJ. Production and characterization of monoclonal antibodies to rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci U S A 79:3734-8, 6/1982. PMID: 6954516.

Invited Articles

1. Stratton SA, Barton MC. p53-mediated regulation of hepatic lipid metabolism: forging links between metabolism, atherogenesis and cancer. J Hepatol 56(3):518-9, 3/2012. e-Pub 10/31/2011. PMID: 22051552.
2. Jain AK, Barton MC. Unmet Expectations: miR-34 Plays No Role in p53-Mediated Tumor Suppression In Vivo. PLoS Genet 8(7):e1002859, 2012. e-Pub 7/26/2012. PMCID: PMC3411369.
3. Mani SA, Barton MC. HDAC3 at the fulcrum of an epithelial-mesenchymal balance. Mol Cell 43(5):697-8, 9/2/2011. PMID: 21884971.
4. Minard ME, Jain AK, Barton MC. Analysis of epigenetic alterations to chromatin during development. Genesis 47(8):559-72, 8/2009. PMCID: PMC2751662.
5. Cirillo LA, Barton MC. Many forkheads in the road to regulation. Symposium on forkhead transcription factor networks in development, signalling and disease. EMBO Rep 9(8). e-Pub 7/2008. PMCID: PMC2515216.
6. Johnson AB and Barton MC. Hypoxia-induced and stress-specific changes in chromatin structure and function. Mutat Res 618(1-2):149-162, 2007. e-Pub 1/21/2007. PMCID: PMC1924842.
7. Barton MC, Akli S, Keyomarsi K. Deregulation of cyclin E meets dysfunction in p53: closing the escape hatch on breast cancer. J Cell Physiol 209(3):686-694, 12/2006. PMID: 17001684.
8. Barton MC. Influences along the path to maturity: regulation of cellular levels of RNA. Biochim Biophys Acta 1759(8-9):385-387, Aug-Sep, 8/2006. e-Pub 9/5/2006. PMID: 17007943.

Last updated: 12/15/2014