Emily Bernstein

Research

Specific Clinical/Research Interest: Our focus is on epigenetic regulation of gene expression in multiple biological pathways including cancer (focus on melanoma) and stem cell biology. This includes various mechanisms that alter the chromatin template, including histone modifications, histone variants and their dedicated chaperones, and non-coding RNAs.

Postdoctoral Fellows:  Chiara Vardabasso, Alexandre Gaspar Maia

Current Students: Hsan-Au (Mooki) Wu, Luis F. Duarte, Chi-Yeh (Jay) Chung, Dan Hasson, Zulekha A. Qadeer

Research Assistant:  Taniya Panda

Summary of Current Research
Epigenetic regulation underlies the commitment of a genomic locus or chromosome (e.g., inactive X) to a particular transcriptional state throughout differentiation and development. This regulation is mediated by various intersecting mechanisms including: histone modifications, histone-modifying enzymes, histone binding proteins, histone variants, DNA methylation, and non-coding RNAs. Epigenetics, in a broad sense, is a bridge between genotype and phenotype - a phenomenon that changes the final outcome of a locus or chromosome without changing the underlying DNA sequence. For example, although the vast majority of cells in a multicellular organism share an identical genotype, the process of development generates numerous cell types with disparate, yet stable profiles of gene expression and distinct cellular functions. Disruption of this epigenetic balance can perturb gene regulation and may lead to disease, notably cancer.

Chromatin is the complex of DNA and its intimately associated proteins -with histones constituting the major component. This template is an attractive candidate for shaping the features of a cell's epigenetic landscape. At the heart of epigenetic gene silencing lay histone H3K27 methylation and the Polycomb Group (PcG) proteins, which are a main focus of the lab. In mammals, there are five homologs of the single Drosophila Pc protein and it has been a longstanding goal to understand the consequences of such expansion and diversification of this protein family in both development and disease. We have previously demonstrated that each individual Pc protein is unique not only in its histone binding-specificity, but also in its association with heterochromatin (in particular, the inactive X chromosome in female mammals). We are also investigating the mechanism of Pc recruitment to chromatin, as this aspect of Pc function is essentially unknown.

A second major focus in the lab is the study of histone variant proteins. When incorporated into chromatin, histone variants participate in diverse nuclear functions including centromeric regulation, DNA damage responses, transcriptional activation and repression, and potentially play a role in epigenetic inheritance of chromatin states. Histone variants alter the structure and stability of the nucleosome, and provide the cell with the potential to change its post-translational modification (PTM) profile due to amino acid sequence differences from their conventional histone counterparts. We are interested in variant-specific PTMs and their binding proteins, as well as the chaperones that escort these proteins in and out of the chromatin template.

Finally, our long-term goal is to understand the chromatin changes that take place at the molecular level during the transformation process of 'normal cells' to 'cancer cells'. Recently, we have uncovered a critical role for histone variants in the progression of malignant melanoma.