Precise regulation of transcription is central to cellular homeostasis and an organism’s response to developmental, nutritional, and environmental signals. Transcription factors bind to DNA to directly regulate gene expression and control cell fate. We develop and adopt molecular genomics approaches to study regulatory cascades initiated by hormone signaling. The lab’s current work focuses on the basic mechanisms of estrogen signaling in breast cancer and how signaling cascades are disrupted upon tamoxifen treatment. We also use integrative genomics approaches to study glucocorticoid-induced apoptosis in glucocorticoid-sensitive and resistant acute lymphocytic leukemia cells. A long-term goal of the lab is to identify transcription factors that are responsible for hormone-resistant phenotypes in cancer cells.
The group is looking to fill two openings: 1) an experimental biologist who will generate genomics data to address fundamental questions about cancer biology and transcriptional regulation; 2) a computational scientist who will development novel methods for interpreting genomics data in the context of transcriptional regulatory networks. Click the appropriate link above for details.
Martins AL, Walavalkar NM, Anderson WD, Zang C, Guertin MJ. Universal correction of enzymatic sequence bias. bioRxiv. doi: https://doi.org/10.1101/104364, 2017. PDF
Duarte DM, Fuda NJ, Mahat DB, Core LJ, Guertin MJ, Lis JT. Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation. Genes and Development 30(15):1731-46, 2016. PDF
Fuda NJ, Guertin MJ, Sharma S, Danko CG, Martins AL, Siepel A, Lis JT. GAGA Factor Maintains Nucleosome-Free Regions and Has a Role in RNA Polymerase II Recruitment to Promoters. PLOS Genetics 11(3): e1005108, 2015. PDF
Guertin MJ, Zhang X, Anguish L, Kim S, Varticovshi L, Lis JT, Hager GL, Coonrod SA. Targeted H3R26 deimination specifically facilitates ER binding by modifying nucleosome structure: PLOS Genetics 10 (9), e1004613, 2014. PDF
Sung M, Guertin MJ, Baek S, Hager GL. DNase footprint signatures are dictated by factor dynamics and DNA sequence: Molecular Cell 56(2): 275-285, 2014. PDF
Guertin MJ, Zhang X Coonrod SA, Hager GL. Transient ER binding and p300 redistribution support a squelching mechanism for E2-repressed genes: Molecular Endocrinology 28(9): 1522-33, 2014. PDF
Guertin MJ, Lis JT. Mechanisms by which transcription factors gain access to target sequence elements in chromatin. Current Opinion in Genetics and Development 23(2): 116-123, 2013. PDF
Guertin MJ, Martins AL, Siepel A, Lis JT. Accurate predictions of inducible transcription factor binding intensities in vivo. PLoS Genetics 8(3): e1002610, 2012. PDF
Zhang X, Bolt M, Guertin MJ, Chen W, Zhang S, Cherrington BD, Slade DJ, Dreyton CJ,Subramanian V, Bicker KL, Thompson PR, Mancini MA, Lis JT, Coonrod SA. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation. Proc Natl Acad Sci 109(33):13331-13336, 2012. PDF
Guertin MJ, Petesch SJ, Zobeck KL, Min IM, Lis JT. Drosophila heat shock system as a general model to investigate transcriptional regulation. Cold Spring Harb Symp Quant Biol. 75:1-9, 2011. PDF
Guertin MJ, Lis JT. Chromatin landscape dictates HSF binding to target DNA elements. PLoS Genetics 6(9):e1001114, 2010. PDF
Carmon A, Guertin MJ, Grushko O, Marshall B, MacIntyre R. A molecular analysis of mutations at the complex dumpy locus in Drosophila melanogaster. PLoS ONE 5(8):e12319, 2010. PDF