Epigenetic Regulatory Mechanisms of Neuron-Specific Gene Expression during Mammalian Development

[국제] Epigenetic Regulatory Mechanisms of Neuron-Specific Gene Expression during Mammalian Development

Seminar title:

Speaker:

Ho Sung Rhee, Ph.D

Associate Professor

Department of Cell & Systems Biology

UNiversity of Toronto, Canada

Abstract

Neuron-specific gene expression is partially established by epigenetic regulatory proteins, including chromatin remodeling complexes that modulate the accessibility of cis

-regulatory DNA elements such as enhancers. Neuron-specific BAF chromatin remodeling complexes contain a non-catalytic subunit, CREST, whose

de novo

mutations have been identified in patients with ALS motor neuron disease. However, the mechanisms by which CREST regulates neuron-specific gene expression during the specification and maintenance of motor neuron identity remain poorly understood. We elucidate the stepwise genomic mechanisms by which CREST regulates motor neuron differentiation from mouse embryonic stem cells. We demonstrate that CREST recognizes enhancers bound by motor neuron-specific transcription factors Onecut1 and Ngn2. Then, CREST selectively recruits the CBP histone acetyltransferase to acetylate histone H3 lysine 27 at neuronal enhancers, leading to the epigenetic activation of mature neuronal genes through long-range chromatin interactions. Moreover, knockout of CREST disrupts the expression of other subunits within the neuronal BAF chromatin remodeling complexes, suggesting that CREST may influence the assembly of these complexes. Our findings uncover a non-canonical function of neuron-specific chromatin remodelers, revealing that CREST mediates communication between epigenetic regulators and neuron-specific enhancers, a mechanism essential for proper neuronal function.

Date:

2025. 04. 14. (Mon.)

Time:

4:30 – 5:45

Location:

생명과학대학관 119호 시청각실