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Author

Vivek Kumar

Bio: Vivek Kumar is an academic researcher from University of Texas Southwestern Medical Center. The author has contributed to research in topics: Circadian clock & Circadian rhythm. The author has an hindex of 22, co-authored 58 publications receiving 4235 citations. Previous affiliations of Vivek Kumar include University of Chicago & Post Graduate Institute of Medical Education and Research.


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
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

Journal ArticleDOI
15 Sep 2000-Cell
TL;DR: Together, these findings suggest that specific combinations of corepressors and histone deacetylases mediate the gene-specific actions of DNA-bound repressors in development of multiple organ systems.

502 citations

Journal ArticleDOI
TL;DR: Chinnadurai et al. as mentioned in this paper showed that minal binding protein (CtBP) is a functional dehy-dehyde-acid dehydrogenase (D2HED) related protein.

271 citations


Cited by
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Journal ArticleDOI
TL;DR: This work discusses knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system and some of the SCN output pathways serve as input pathways for peripheral tissues.
Abstract: Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.

1,984 citations

Journal ArticleDOI
TL;DR: This review focuses on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling.
Abstract: During the past decade there has been a substantial advance in our understanding of estrogen signaling both from a clinical as well as a preclinical perspective. Estrogen signaling is a balance bet...

1,652 citations

Journal ArticleDOI
TL;DR: High-resolution multiorgan expression data is generated showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body, and the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes.
Abstract: To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional “rush hours” preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.

1,642 citations

Journal ArticleDOI
TL;DR: The general mechanisms of the circadian clockwork are reviewed, recent findings that elucidate tissue-specific expression patterns of the clock genes are described and the importance of circadian regulation in peripheral tissues for an organism's overall well-being is addressed.
Abstract: Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases. Signals that can entrain these peripheral clocks include humoral signals, metabolic factors, and body temperature. At the level of individual tissues, thousands of genes are brought to unique phases through the actions of a local transcription/translation-based feedback oscillator and systemic cues. In this molecular clock, the proteins CLOCK and BMAL1 cause the transcription of genes which ultimately feedback and inhibit CLOCK and BMAL1 transcriptional activity. Finally, there are also other molecular circadian oscillators which can act independently of the transcription-based clock in all species which have been tested.

1,550 citations

Journal ArticleDOI
TL;DR: Genome-wide analyses of the clock transcriptional feedback loop have revealed a global circadian regulation of processes such as transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription, and chromatin remodelling.
Abstract: Circadian clocks are endogenous oscillators that control 24-hour physiological and behavioural processes in organisms. These cell-autonomous clocks are composed of a transcription-translation-based autoregulatory feedback loop. With the development of next-generation sequencing approaches, biochemical and genomic insights into circadian function have recently come into focus. Genome-wide analyses of the clock transcriptional feedback loop have revealed a global circadian regulation of processes such as transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription, and chromatin remodelling. The genomic targets of circadian clocks are pervasive and are intimately linked to the regulation of metabolism, cell growth and physiology.

1,538 citations