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实验室

10:00-12:00, Monday, April 9, 2018

A-Type Seminar

Location: Auditorium

Time:    10:00-12:00, Monday, April 9, 2018

Speaker1: Carla B. Green,
Ph.D.Professor,
Department of Neuroscience,
University of Texas Southwestern Medical Center,
5323 Harry Hines Blvd., ND4.124A,
Dallas TX 75390-9111

Topic:     Transcriptional and Post-transcriptional Regulation of Metabolism by the Circadian Clock


Abstract

The timing of food intake and nutrient utilization is critical to health and extensively regulated by the circadian clock. The mechanism involves both through transcriptional control, via direct and indirect regulation of metabolic genes by the core clock components, and through post-transcriptional control of mRNA levels and translation.   We have used evolutionary sequence analysis approaches to identify co-evolving residues within the circadian repressor proteins Cryptochromes to understand the structural principles of transcriptional regulation by the core circadian clock, revealing novel allosteric mechanisms that determine period length.  We have also examined post-transcriptional regulation of metabolism through changes in poly(A) tail length, revealing a role in the regulation of amplitude of critical metabolic pathways.

Speaker2: Joseph S. Takahashi, Ph.D.
Howard Hughes Medical Institute,
Department of Neuroscience,
UT Southwestern Medical Center,
Dallas, TX 75390-9111, USA

Topic:     Transcriptional Architecture and Chromatin Landscape of the Circadian Clock System in Mammals

Host:     Erquan Zhang, Ph.D.

Abstract
The molecular mechanism of circadian clocks in mammals is generated by a set of genes forming a transcriptional autoregulatory feedback loop. The “core clock genes” include: Clock, Bmal1, Per1, Per2, Cry1 and Cry2. The discovery of “clock genes” led to the realization that circadian gene expression is widespread throughout the body and that the clock is cell autonomous. The cellular autonomy of circadian clocks has raised a number of questions concerning synchronization and coherence of rhythms at the cellular level as well as circadian organization at the systems level. The role of clocks in peripheral tissues has a number of important implications for disease. In the circadian clock mechanism, CLOCK and BMAL1 activate the transcription of the Period and Cryptochrome genes. The PERIOD and CRYPTOCHROME proteins then feedback and repress their own transcription by interaction with CLOCK and BMAL1. In the mouse liver, CLOCK and BMAL1 interact with the regulatory regions of thousands of genes, which are both cyclically and constitutively expressed. These target genes are highly enriched for metabolic pathways and indeed all fundamental metabolic pathways in the cell are direct targets of CLOCK:BMAL1. In addition to transcriptional control, the circadian system impacts the timing of metabolism with respect to body weight regulation, aging and longevity. These topics will also be discussed.