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Seminar in Molecular Cell Biology

Date: 
March 7, 2016 - 3:00pm to 5:00pm

Lineage stability and functional plasticity of regulatory T cells - an iron fist in a velvet glove

Dr. Xudong Li

The homeostasis of multicellular organisms requires terminally differentiated cells to preserve their lineage specificity. However, it is unclear whether mechanisms exist to actively protect cell identity in response to environmental cues that confer functional plasticity. Regulatory T (Treg) cells, specified by the transcription factor Foxp3, are indispensable for immune system homeostasis. Here, we report that conserved noncoding sequence 2 (CNS2), a CpG-rich Foxp3 intronic cis-element specifically demethylated in mature Tregs, helps maintain immune homeostasis and limit autoimmune disease development by protecting Treg identity in response to signals that shape mature Treg functions and drive their initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression from destabilizing cytokine conditions by sensing TCR/NFAT activation, which facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically marked cis-elements can protect cell identity by sensing key environmental cues central to both cell identity formation and functional plasticity without interfering with initial cell differentiation.

Location: 
Classroom and Office Building, Room 120
Name: 
Jennifer Manilay
Title: 
Associate Professor
Department: 
Molecular Cell Biology, School of Natural Sciences
Address: 
5200 North Lake Rd.
Merced, CA 95343
United States
Address: 
5200 North Lake Rd.
Merced, CA 95343
United States