Kathrin Muegge, M.D.
- Center for Cancer Research
- National Cancer Institute
- Building 560, Room 32-31B
- Frederick, MD 21702-1201
Dr. Muegge studies molecular mechanisms that alter chromatin structure and function during development. She discovered several links between chromatin modifiers, including nucleosome remodeling, histone variants, chromatin accessibility and DNA methylation.
The current focus is to understand how mutations of the chromatin remodeler LSH perturb the process of recombination and DNA repair in the genetic ICF4 syndrome.
Areas of Expertise
1) nucleosome remodeling 2) histone variants 3) DNA methylation 4) cellular differentiation 5) genome stability 6) murine development
Lsh, a Guardian of Heterochromatin
Epigenetic modifications comprise histone modifications, histone variants, nucleosome occupancy and DNA methylation and are crucial for organization of the genome into active chromatin (euchromatin) and repressed chromatin (heterochromatin). The functional organization of chromatin is important for regulation of transcription, cellular differentiation, and genome maintenance. Our group studies the role of epigenetic modifications that control chromatin structure during normal embryonic development and in human disease.
The current focus of our studies is to understand the molecular mechanisms and biological role of LSH (Lymphoid specific helicase) that my group has discovered. LSH or HELLS (Helicase, lymphoid specific) is an ATPase dependent SNF2 family member and is critical for murine development. LSH mutation in human cause the ICF4 syndrome a complex disease with immunodeficiency, centromeric instability and facial anomalies.
Our recent work indicates that LSH induces deposition of macroH2A in the genome and acts a histone variant exchange factor. We are currently addressing the question of how LSH molecular function alters chromatin structure and influences genomic stability and cellular differentiation. These studies should provide insights into a number of basic biologic processes that involve epigenetic modifications such as transcription, DNA repair, replication and recombination.
LSH catalyzes ATP-driven exchange of histone variants macroH2A1 and macroH2A2
The epigenetic regulator LSH maintains fork protection and genomic stability via MacroH2A deposition and RAD51 filament formation.
Kathrin Muegge, M.D.
Dr. Muegge obtained her M.D. degree at the Medical School Hannover, Germany. During her postdoctoral period she worked on cytokines and T cell development in the Laboratory of Molecular Immunoregulation of Dr. Joost Oppenheim and Dr. Scott Durum. As a Principal Investigator at the National Cancer Institute in Frederick, she now investigates in the Mouse Cancer Genetics Program chromatin organization during development and in human disease.
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