Description:

Nucleosomes: From Pioneer Factors to Occupancy Dynamics in Aged Liver by Irina Bochkis, PhD

The Department of Biochemistry and Molecular Genetics would like to invites faculty, students, and staff to attend a research presentation featuring Irina Bochkis, PhD, Postdoctoral Associate, Broad Institute of Harvard and MIT.

Presentation Abstract:
Previous studies suggest a role for chromatin and nuclear organization in aging-associated lipid dystrophies. Liver-specific loss of Foxa2, a pioneer transcription factor regulating nucleosome dynamics, leads to premature aging, increased hepatic lipogenesis, and age-onset obesity. To study the role of chromatin organization in modulating age-dependent metabolic impairments in a model of physiological aging we examined gene expression and genome-wide nucleosome occupancy in livers isolated from young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix transcription factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged livers.