The Epigenetics Section studies chromatin structure and function and how chromatin regulates DNA access and, thus, controls biological processes. 

Our scientists focus on murine development, in particular how the chromatin remodeling protein LSH affects development. Our team is affiliated with and provides chromatin biology expertise to the Mouse Cancer Genetics Program of the National Cancer Institute's Center for Cancer Research. 

Understanding the genome 

Chromatin is a critical component of the genome’s structure, and changes to chromatin or its functions can affect how embryos develop. We investigate the effects of epigenetic chromatin modifications to better understand chromatin's connections to disease and normal embryonic development.

Key to T-dependent B cell responses

Absence of HELLS leads to appearance of memory-B cell markers or metabolic state change

Germinal center output is sustained by HELLS-dependent DNA methylation maintenance in B cells.
Chromatin remodeler

LSH catalyzes ATP-driven exchange of macroH2A1 and macroH2A2

Results show a previously unknown role for LSH in chromatin remodeling.

An authority in the field 

We discovered LSH in the 1990s and have remained interested in its functions and roles ever since, regularly conducting new studies to better understand it. Our scientists recently used a mouse model in which the LSH gene in lymphocytes was turned off to reveal the process behind these altered immune cells’ inability to produce new antibody types.

Some of our other research showed that LSH is vital for depositing macroH2A in the genome and influencing the composition of chromatin. This work identified a complex molecular pathway that contributes to ICF syndrome type 4, a rare genetic disorder caused by a mutation in the human LSH homologue. 

 

Examining chromatin and its functions

The Epigenetics group investigates the molecular mechanisms that recruit LSH to chromatin, assesses which co-factors help LSH alter chromatin, and examines how changes in 3D chromatin structure influence DNA repair and recombination.  

Chromatin remodeling 

We study chromatin remodeling by determining the molecular mechanisms by which the chromatin remodeling protein LSH alters chromatin structure in the mouse genome and influences gene function. We analyze the deposition of histone variant macroH2A by LSH.

LSH Pathways 

We study LSH's role in genomic stability by investigating the pathways that cause susceptibility to replication stress and genomic instability upon LHS deletion and by examining changes in the chromatin environment at stalled replication forks that prevent or promote DNA breaks.

Causes of immunodeficiency 

To investigate the causes of immunodeficiency, we study the B-cell competency defect that occurs upon LSH deletion and the ICF4 syndrome caused by LSH mutations to characterize the role of LSH-mediated chromatin changes in immunoglobulin class switch recombination.