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Author

Choogon Lee

Bio: Choogon Lee is an academic researcher from Florida State University. The author has contributed to research in topics: Circadian clock & Circadian rhythm. The author has an hindex of 35, co-authored 49 publications receiving 8522 citations. Previous affiliations of Choogon Lee include Harvard University & University of Massachusetts Medical School.


Papers
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Journal ArticleDOI
19 Oct 2012-Science
TL;DR: The transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver is interrogated and a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II recruitment, RNA expression, and chromatin states is found.
Abstract: The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment, RNA expression, and chromatin states. We find that the circadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.

1,184 citations

Journal ArticleDOI
28 Dec 2001-Cell
TL;DR: Analysis of clock proteins in m CRY-deficient mice shows that the mCRYs are necessary for stabilizing phosphorylated mPER2 and for the nuclear accumulation of mPER1, mper2, and CKIepsilon, and provides in vivo evidence that casein kinase I delta is a second clock relevant kinase.

1,114 citations

Journal ArticleDOI
01 May 2009-Science
TL;DR: It is reported that both the rate-limiting enzyme in mammalian Nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice.
Abstract: The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle. Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1.

987 citations

Journal ArticleDOI
09 Jan 2003-Nature
TL;DR: It is shown that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone acetylation, and that H3 acetylations is a potential target of the inhibitory action of Cry.
Abstract: In the mouse circadian clock, a transcriptional feedback loop is at the centre of the clockwork mechanism. Clock and Bmal1 are essential transcription factors that drive the expression of three period genes (Per1-3) and two cryptochrome genes (Cry1 and Cry2). The Cry proteins feedback to inhibit Clock/Bmal1-mediated transcription by a mechanism that does not alter Clock/Bmal1 binding to DNA. Here we show that transcriptional regulation of the core clock mechanism in mouse liver is accompanied by rhythms in H3 histone acetylation, and that H3 acetylation is a potential target of the inhibitory action of Cry. The promoter regions of the Per1, Per2 and Cry1 genes exhibit circadian rhythms in H3 acetylation and RNA polymerase II binding that are synchronous with the corresponding steady-state messenger RNA rhythms. The histone acetyltransferase p300 precipitates together with Clock in vivo in a time-dependent manner. Moreover, the Cry proteins inhibit a p300-induced increase in Clock/Bmal1-mediated transcription. The delayed timing of the Cry1 mRNA rhythm, relative to the Per rhythms, is due to the coordinated activities of Rev-Erbalpha and Clock/Bmal1, and defines a new mechanism for circadian phase control.

656 citations

Journal ArticleDOI
01 Jun 2007-Cell
TL;DR: Fbxl3(Ovtm) defines a molecular link between CRY turnover and CLOCK/BMAL1-dependent circadian transcription to modulate circadian period.

517 citations


Cited by
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Journal ArticleDOI
29 Aug 2002-Nature
TL;DR: Circadian rhythms are generated by one of the most ubiquitous and well-studied timing systems and are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.
Abstract: Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.

3,962 citations

Journal ArticleDOI
Jay C. Dunlap1
22 Jan 1999-Cell
TL;DR: It used to be that research in chronobiology moved biochemical functions [transcriptional activators], the along at a gentlemanly pace, but by mid 1997 the word in determining what the authors perceive as time was PASWCCLK.

2,723 citations

Journal ArticleDOI
30 Mar 2012-Cell
TL;DR: The richness of the understanding of MYC is reviewed, highlighting new biological insights and opportunities for cancer therapies.

2,572 citations

Journal ArticleDOI
26 Jul 2002-Cell
TL;DR: The orphan nuclear receptor REV-ERBalpha is identified as the major regulator of cyclic Bmal1 transcription, and constitutes a molecular link through which components of the negative limb drive antiphasic expression of component of the positive limb.

2,052 citations

01 Mar 2017
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR-signaling network contributes to human disease is highlighted.
Abstract: The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.

2,014 citations