Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Puram, Rishi V.; Kowalczyk, Monika S.; Boer, Carl G. de; Schneider, Rebekka K.; Miller, Peter G.; McConkey, Marie; Tóthová, Zuzana; Tejero, Héctor; Heckl, Dirk; Järås, Marcus; Chen, Michelle C.; Li, Hubo; Tamayo, Alfred; Cowley, Glenn S.; Rozenblatt-Rosen, Orit; Al‐Shahrour, Fátima; Regev, Aviv; Ebert, Benjamin L.

doi:10.1016/j.cell.2016.03.015

Cited by 202 publications

(178 citation statements)

References 79 publications

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“…Indeed, genetic variations in core clock genes have been shown to be associated with numerous metabolic diseases, cancers, sleep disorders and mental disorders (11). Animal models revealed that core clock genes are involved in sleep and mood regulation, as well as the development of obesity, diabetes and cancer (7,12–15). At the molecular level, ∼1% to over 60% of the transcriptome exhibits oscillatory expression, and the majority of the best-selling drugs as well as essential medicines of World Health Organization target cycling genes (1,16,17).…”

Section: Introductionmentioning

confidence: 99%

OUP accepted manuscript

Shui

Zhang

et al. 2016

Nucleic Acids Research

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We report a database of circadian genes in eukaryotes (CGDB, http://cgdb.biocuckoo.org), containing ∼73 000 circadian-related genes in 68 animals, 39 plants and 41 fungi. Circadian rhythm is ∼24 h rhythm in behavioral and physiological processes that exists in almost all organisms on the earth. Defects in the circadian system are highly associated with a number of diseases such as cancers. Although several databases have been established for rhythmically expressed genes, a comprehensive database of cycling genes across phyla is still lacking. From the literature, we collected 1382 genes of which transcript level oscillations were validated using methods such as RT-PCR, northern blot and in situ hybridization. Given that many genes exhibit different oscillatory patterns in different tissues/cells within an organism, we have included information regarding the phase and amplitude of the oscillation, as well as the tissue/cells in which the oscillation was identified. Using these well characterized cycling genes, we have then conducted an orthologous search and identified ∼45 000 potential cycling genes from 148 eukaryotes. Given that significant effort has been devoted to identifying cycling genes by transcriptome profiling, we have also incorporated these results, a total of over 26 000 genes, into our database.

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Section: Introductionmentioning

confidence: 99%

OUP accepted manuscript

Shui

Zhang

et al. 2016

Nucleic Acids Research

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“…This interconnection between disrupted clocks and cancer was demonstrated recently in an adenocarcinoma mouse model, whereby the tumours impacted on clock-control of liver lipid metabolism [52]. In a mouse model of acute myeloid leukemia (AML), knockdown of Bmal1 and Clock in mouse leukemia cells depleted the pool of leukemic stem cells and reduced proliferation [53]. A REV-ERB␣ and REV-ERB␤ agonist repressed Bmal1 and inhibited viability of both mouse and human AML cells.…”

Section: Circadian Disruption and Diseasementioning

confidence: 99%

Immunometabolism: Is it under the eye of the clock?

Early

Curtis

2016

Seminars in Immunology

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“…The maintenance or disruption of circadian rhythms contribute significantly to several areas of health and disease ( Asher & Schibler, 2011; Chen & Yang, 2015; Puram et al , 2016; Roenneberg & Merrow, 2016; Sahar & Sassone-Corsi, 2009; Takahashi et al , 2008). Circadian rhythms are daily biological rhythms synchronized by light and dark cycles of the day/night continuum.…”

Section: Introductionmentioning

confidence: 99%

A simple method to measure CLOCK-BMAL1 DNA binding activity in tissue and cell extracts

Gillessen

Kwak²,

Tamayo³

2017

F1000Res

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The proteins CLOCK and BMAL1 form a heterodimeric transcription factor essential to circadian rhythms in mammals. Daily rhythms of CLOCK-BMAL1 DNA binding activity are known to oscillate with target gene expression in vivo. Here we present a highly sensitive assay that recapitulates native CLOCK-BMAL1 DNA binding rhythms from crude tissue extracts, which we call the Clock Protein-DNA Binding Assay (CPDBA). This method can detect less than 2-fold differences in DNA binding activity, and can deliver results in two hours or less using 10 microliters or less of crude extract, while requiring neither specialized equipment nor expensive probes. To demonstrate the sensitivity and versatility of this assay, we show that enzymatic removal of phosphate groups from proteins in tissue extracts or pharmacological inhibition of casein kinase I in cell culture increased CLOCK-BMAL1 DNA binding activity by ~1.5 to ~2 fold, as measured by the CPDBA. In addition, we show that the CPDBA can measure CLOCK-BMAL1 binding to reconstituted chromatin. The CPDBA is a sensitive, fast, efficient and versatile probe of clock function.

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Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Cited by 202 publications

References 79 publications

OUP accepted manuscript

OUP accepted manuscript

Immunometabolism: Is it under the eye of the clock?

A simple method to measure CLOCK-BMAL1 DNA binding activity in tissue and cell extracts

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