2016 Scientific Report

Mechanisms regulating the inheritance of DNA
methylation
Application of microarray technology to the
study of histone PTMs.
The faithful inheritance of DNA methylation patterns is
essential for normal mammalian development and long-term
transcriptional silencing. We recently discovered that
the E3 ubiquitin ligase UHRF1 is a key regulator of this
process through its interaction with a histone signature of
transcriptionally silent heterochromatin. Current studies are
focused on defining the molecular interconnections between
UHRF1, DNMTs, and chromatin, and on elucidating the role of
UHRF1 deregulation in tumor initiation and progression.
We recently developed a histone peptide microarray platform
that has greatly improved our understanding of histone
PTM function in development and disease, as well as during
the fundamental processes of transcription, chromatin
organization, and DNA repair. We are developing several
new microarray-based platforms to enable high-throughput
discovery of histone PTM function. Two areas of focus are
to expand the utility of our current histone peptide array in
defining the influence of the “histone code” on writers and
erasers of these marks and to develop a multiplex array assay
for comparative profiling of histone PTM patterns in stages of
differentiation and disease.
RECENT PUBLICATIONS
Rothbart, Scott B., Bradley M. Dickson, Jesse R. Raab, Adrian T. Grzybowski, Krzysztof Krajewski, Angela H. Guo, Erin K. Shanle,
Steven Z. Josefowicz, Stephen M. Fuchs, et al. 2015. An interactive database for the assessment of histone antibody specificity.
Molecular Cell 59(3): 502–511.
Simon, Jeremy M., Joel S. Parker, Feng Liu, Scott B. Rothbart, Slimane Ait-Si-Ali, Brian D. Strahl, Jian Jin, Ian J. Davis,
Amber L. Moseley, and Samantha G. Pattenden. 2015. A role for widely interspaced zinc finger (WIZ) in retention of the G9a
methyltransferase on chromatin. Journal of Biological Chemistry 290(43): 26088–26102.
Zhang, Zhi-Min, Scott B. Rothbart, David F. Allison, Qian Cai, Joseph S. Harrison, Lin Li, Yinsheng Wang, Brian D. Strahl, Gang
Greg Wang, and Jikui Song. 2015. An allosteric interaction links USP7 to deubiquitination and chromatin targeting of UHRF1.
Cell Reports 12(9): 1400–1406.
CENTER FOR EPIGENETICS
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