Shi Laboratory

Yang Shi, Principal Investigator

The Shi Lab is interested in epigenetic mechanisms that control gene expression and other chromatin template-based nuclear events and how they impact biological processes and human health.

Research Summary
Epigenetics refers to changes in gene expression that do not involve changes in DNA sequences. A distinguishing feature of epigenetic regulation is the ability to offer both stability and flexibility as mechanisms for controlling gene expression, contrary to genetic regulation, which is irreversible. Consequently, epigenetic regulation likely functions as a dynamic conduit for interaction between a cell/organism and its surrounding environment.

A major component of epigenetic regulation occurs in chromatin, where covalent and non-covalent modifications can lead to heritable changes in gene expression. The basic unit of chromatin is the nucleosome, which is composed of 146 base pairs of DNA that wrap around a histone octamer, including two copies of histones H2A, H2B, H3 or H4.  Both DNA and histone are chemically modified. The cytosine of DNA can be methylated and hydroxymethylated, and CpG methylation has been shown to play a critical role in epigenetic regulation. Histones are modified extensively at N-terminal tails via phosphorylation, acetylation, methylation, and ubiquitination.

The Shi Lab is interested in studying histone methylation as a steady yet revocable process, supported by Yang Shi’s research and discovery of histone demethylases, as well as other components of epigenetic regulatory mechanisms.

The Lab is interested in understanding the following:
1. How epigenetic changes can propagate from one generation to another.

2. What the molecular mechanisms are which ensure stability and reversibility of epigenetic information. More specifically:
- How chemical modifications (e.g. methylation) are put onto chromatin
- How modifications (i.e. histone and DNA methylation) are removed
- How combinatorial modifications of chromatin are recognized by effector proteins

3. How chromatin modifications translate into specific biological processes and thus impact human health, particularly how said epigenetic regulations relate to neural development and cancer.