ATP-Dependent Remodeling of Hexasomes, Nucleosomes and Chromatin Condensates - Geeta Narlikar

ATP-dependent chromatin remodeling complexes play critical roles on regulating access to DNA. Many remodeling complexes act on the smallest unit of chromatin, a nucleosome. Howeve, our recent work has indicated that unlike other chromatin remodeling complexes, the INO80 complex preferentially mobilizes subnucleosomal particles called hexasomes, which are formed during transcription. Why INO80 prefers hexasomes over nucleosomes remains unclear. Additionally, how the action of chromatin remodeling complexes at the nucleosome scale impacts higher-order chromatin organization is not well-understood. We find that preferential hexasome sliding by INO80 relies on novel mechanistic adaptations that slow the sliding of nucleosomes. We also find that the action of chromatin remodelers in phase-separated chromatin condensates causes decompaction of the condensates. In this talk, Dr. Narlikar will share these and additional results where we are uncovering new types of biologically relevant activities of chromatin remodeling enzymes.

About Geeta Narlikar
Dr. Narlikar obtained her Ph.D. in Chemistry at Stanford University under the mentorship of Dr. Daniel Herschlag and carried out postdoctoral research at Harvard Medical School under the mentorship of Dr. Robert Kingston. She has been a faculty member in the Department of Biochemistry and Biophysics at UCSF since 2003. She is an expert in the fields of epigenetic regulation and genome organization. Dr. Narlikar studies how the folding and compartmentalization of our genome is regulated to generate the many cell types that make up our body. Her laboratory has pioneered the application of sophisticated biophysical approaches to study the mechanisms of macromolecules that regulate genome organization. Through these studies they are learning (i) how nanoscale molecular motors use chemical energy to cause mechanical disruptions in the packaged genome, (ii) that the smallest unit of genome folding, a nucleosome, acts akin to a dynamic receptor rather than a static packaging unit and, (iii) that liquid-liquid phase separation processes can help organize and sequester large regions of the genome. These types of discoveries from the Narlikar laboratory are changing textbook descriptions of genome packaging and suggesting new avenues to tackle diseases caused by defects in genome organization. Dr. Narlikar enjoys teaching and mentoring graduate students. She believes that kindling the fire of curiosity within graduate students and consistently supporting their initiative brings out the best in them. Dr. Narlikar’s scientific work has been recognized by different awards during the course of her faculty career. These include the Beckman Young Investigator Award (2006), the Leukemia and Lymphoma Society Scholar Award (2008), the Outstanding Faculty Mentorship Award by the UCSF Graduate Students Association (2011), the Glenn Award for Research in Biological Mechanisms of Aging (2018), and the Distinguished Alumnus Award from the Indian Institute of Technology, Mumbai (2018). She was elected to the National Academy of Sciences in 2021 and the American Academy of Arts and Sciences in 2024.

The Monthly Seminar on Physical Genomics is a public lecture series sponsored by the Center for Physical Genomics at Northwestern University, the Robert H. Lurie Comprehensive Cancer Center, and NIH Grants T32GM142604 and U54CA268084.

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