In the last few years, our lab’s research has advanced our understanding of how enhancer landscapes and epigenetic mechanisms shape the expression profiles of cancer-associated gene networks that are linked to enhanced tumor development and metastatic progression.
Our research has revealed a new mechanism in which mutp53 together with the histone monomethyltransferase MLL4 gives rise to alterations in the deposition of histone H3 lysine 4 monomethylation (H3K4me1), which is a histone modification that is frequently altered in various human cancers. We also revealed that these changes in the chromatin environment promote cancer cell migration and invasion through the potent activation of a subset of mutp53 target genes.
Characterized a new role for the basal transcription factor TFIID complex in cellular signaling during muscle development
1. Revealed a new regulatory mechanism to describe how chronic immune signaling fuels cancer cell growth
2. Identified new mechanistic insights into how epigenetic modifications in cancer are established
3. Are at the forefront of uncovering new
mechanistic insights into the functions of a class of significantly understudied
noncoding molecules referred to as enhancer RNAs (eRNAs)
Rahnamoun H, Lee J, Sun Z, Lu H, Ramsey KM, Komives EA, and Lauberth SM. RNAs Interact with BRD4 to Promote Enhanced Chromatin Engagement and Transcription Activation. Nature Structural and Molecular Biology 2018, August 3, 25(8):687-697. PubMed PMID: 30076409.
Homa Rahnamoun, Hanbin Lu, Sascha H. Duttke, Christopher K. Glass, Christopher Benner, and Shannon M. Lauberth. Mutant p53 shapes the enhancer landscape of cancer cells in response to chronic immune signaling. Nature Communications 2017 September 29, 8(1):754. PubMed PMID: 28963538; PubMed Central PMCID: PMC5622043
Stijf-Bultsma Y., Sommer L., Tauber M., Baalbaki M., Giardoglou P., Jones DR., Gelato KA., Van Pelt J., Shah Z., Rahnamoun H., Toma C., Anderson KE., Hawkins P., Lauberth SM., Haramis AG., Hart D., Fischle W., and Divecha N. (2015). The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output. Molecular Cell. doi:10.1016/j.molcel.2015.03.009https://www.sciencedirect.com/science/article/pii/S1097276515001744
Lauberth SM., Nakayama T., Wu X., Ferris A., Tang, Z., Hughes S.H., and Roeder, R.G. (2013).H3K4me3 Interactions with TAF3 Regulate Preinitiation Complex Assembly and Selective Gene Activation. Cell, 1021-1036.
​
J. Biol. Chem.
Lauberth SM., Bilyeu A.C., Firulli, B.A., Kroll K.L., and Rauchman M. (2007). A phosphomimetic mutation in the Sall1 repression motif disrupts recruitment of the nucleosome remodeling and deacetylase complex and repression of Gbx2. J. Biol. Chem. 282, 34858-68.
Lauberth SM., and Rauchman M. (2006). A conserved 12-amino acid motif in Sall1 recruits the nucleosome remodeling and deacetylase corepressor complex. J. Biol. Chem. 281, 23922-31.
