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Article ; Online: Cell-Based Phenotypic Screens to Discover Circadian Clock-Modulating Compounds.

Hatori, Megumi / Hirota, Tsuyoshi

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2482, Page(s) 95–104

Abstract: There is increasing demand to control circadian clock functions in a conditional manner for deeper understanding of the circadian system as well as for potential treatment of clock-related diseases. Small-molecule compounds provide powerful tools to ... ...

Abstract	There is increasing demand to control circadian clock functions in a conditional manner for deeper understanding of the circadian system as well as for potential treatment of clock-related diseases. Small-molecule compounds provide powerful tools to reveal novel functions of target proteins in the circadian clock mechanism, and can be great therapeutic candidates. Here we describe the detailed methods of measuring cellular circadian rhythms in a high-throughput manner for chemical screening to identify compounds that affect circadian rhythms by targeting clock-related proteins.
MeSH term(s)	CLOCK Proteins ; Circadian Clocks/genetics ; Circadian Rhythm
Chemical Substances	CLOCK Proteins (EC 2.3.1.48)
Language	English
Publishing date	2022-05-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2249-0_6
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Article: [Aging and homeostasis. Circadian rhythms and aging.]

Hatori, Megumi

Clinical calcium

2017 Volume 27, Issue 7, Page(s) 955–961

Abstract: Daily rhythms of physiological and behavioral processes such as sleep and arousal are controlled by the circadian clock. The expression of the clock genes oscillate rhythmically in daily manner, and this clock oscillator resides in almost all of the ... ...

Abstract	Daily rhythms of physiological and behavioral processes such as sleep and arousal are controlled by the circadian clock. The expression of the clock genes oscillate rhythmically in daily manner, and this clock oscillator resides in almost all of the cells in the body. The circadian clock entrains to diurnal environmental changes by using light and food intake as external time cues. Timing of feeding and fasting strongly affects daily rhythms in the expression of circadian clock genes and key regulators of nutrient homeostasis. Understanding roles of the clock oscillator system and feeding-fasting cycles lets us recognize the importance of timing of feeding, ultimately to adjust the aging-related changes in circadian rhythms.
Language	Japanese
Publishing date	2017
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa1707955961
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Zs.A 6536: Show issues

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Article: Crosstalk of the circadian clock, light response, feeding and aging.

Tsuyama, Jun / Hatori, Megumi

Nihon rinsho. Japanese journal of clinical medicine

2018 Volume 74, Issue 9, Page(s) 1474–1478

Abstract: Daily rhythms of many physiological and behavioral processes such as sleep and arousal are controlled by the circadian clock. The circadian clock entrains to environmental diurnal changes by using light and food intake as external time cues. Circadian ... ...

Abstract	Daily rhythms of many physiological and behavioral processes such as sleep and arousal are controlled by the circadian clock. The circadian clock entrains to environmental diurnal changes by using light and food intake as external time cues. Circadian photoentrainment is mediated by retinal ganglion cells expressing a blue-light sensitive photopigment mela- nopsin. Feeding and fasting drive daily rhythms in the expression of circadian clock genes and key regulators of nutrient homeostasis in peripheral tissues. Understanding melanopsin function and timing of feeding-fasting lets us recognize the importance of timing of blue light exposure and feeding based on the concept of the circadian clock, ultimately to adjust the age-related changes in daily rhythm.
MeSH term(s)	Aging/physiology ; Animals ; Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Eating ; Humans ; Light ; Sleep
Language	Japanese
Publishing date	2018-12-17
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
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Zs.A 429: Show issues

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Article ; Online: Response of peripheral rhythms to the timing of food intake.

Hatori, Megumi / Panda, Satchidananda

Methods in enzymology

2015 Volume 552, Page(s) 145–161

Abstract: Metabolism and physiology in animals show diurnal rhythm to adapt to the daily cycles of activity-rest and the associated rhythm in feeding and fasting. Accordingly, gene expression, protein activities, and numerous metabolites show daily rhythm in ... ...

Abstract	Metabolism and physiology in animals show diurnal rhythm to adapt to the daily cycles of activity-rest and the associated rhythm in feeding and fasting. Accordingly, gene expression, protein activities, and numerous metabolites show daily rhythm in abundance. The significance of these rhythms in promoting healthy lifespan and preventing disease has recently come to light. Mice with genetic disruption of circadian rhythm, mice, and humans under shift-work paradigm, and mice fed high-fat diet ad libitum exhibit chronic disruption of feeding-fasting rhythm and dampened daily rhythms in physiology, metabolism, and gene expression. These dampened rhythms are associated with metabolic diseases. Conversely, time-restricted feeding, in which mice are fed for certain number of hours every day, restores rhythms and can prevent obesity and metabolic diseases even when mice are fed high-fat diet. These observations seek mechanistic explanations, which will require careful experiments in which feeding duration, genotype, nutrient, and feeding time relative to light:dark cycle will be manipulated and molecular changes in peripheral organs and a few brain regions will be assessed. This chapter will primarily focus on the use of mouse as an experimental animal and the experimental setup so that the molecular readouts can be better interpreted.
MeSH term(s)	Animals ; Circadian Rhythm ; Diet ; Feeding Behavior ; Mice ; Mice, Inbred Strains
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1557-7988 ; 0076-6879
ISSN (online)	1557-7988
ISSN	0076-6879
DOI	10.1016/bs.mie.2014.10.027
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Article ; Online: Nucleosome dynamics regulate Neurospora circadian clock.

Hatori, Megumi / Panda, Satchidananda

EMBO reports

2013 Volume 14, Issue 10, Page(s) 854–855

MeSH term(s)	Adenosine Triphosphatases/metabolism ; Circadian Clocks/genetics ; Fungal Proteins/metabolism ; Neurospora crassa/genetics ; Nucleosomes/metabolism
Chemical Substances	FRQ protein, Neurospora crassa ; Fungal Proteins ; Nucleosomes ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2013-09-13
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.1038/embor.2013.143
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 41: Show issues

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Article ; Online: Sustained Melanopsin Photoresponse Is Supported by Specific Roles of β-Arrestin 1 and 2 in Deactivation and Regeneration of Photopigment.

Mure, Ludovic S / Hatori, Megumi / Ruda, Kiersten / Benegiamo, Giorgia / Demas, James / Panda, Satchidananda

Cell reports

2018 Volume 25, Issue 9, Page(s) 2497–2509.e4

Abstract: Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are indispensable for non-image-forming visual responses that sustain under prolonged illumination. For sustained signaling of ipRGCs, the melanopsin photopigment must ... ...

Abstract	Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are indispensable for non-image-forming visual responses that sustain under prolonged illumination. For sustained signaling of ipRGCs, the melanopsin photopigment must continuously regenerate. The underlying mechanism is unknown. We discovered that a cluster of Ser/Thr sites within the C-terminal region of mammalian melanopsin is phosphorylated after a light pulse. This forms a binding site for β-arrestin 1 (βARR1) and β-arrestin 2. β-arrestin 2 primarily regulates the deactivation of melanopsin; accordingly, βαrr2
MeSH term(s)	Adaptation, Ocular/radiation effects ; Amino Acid Sequence ; Animals ; Animals, Newborn ; Behavior, Animal ; CHO Cells ; Cricetinae ; Cricetulus ; Humans ; Light ; Light Signal Transduction ; Mice ; Models, Biological ; Regeneration/radiation effects ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/radiation effects ; Rod Opsins/chemistry ; Rod Opsins/metabolism ; beta-Arrestin 1/metabolism ; beta-Arrestin 2/metabolism
Chemical Substances	Rod Opsins ; beta-Arrestin 1 ; beta-Arrestin 2 ; melanopsin
Language	English
Publishing date	2018-11-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2018.11.008
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Article ; Online: The emerging roles of melanopsin in behavioral adaptation to light.

Hatori, Megumi / Panda, Satchidananda

Trends in molecular medicine

2010 Volume 16, Issue 10, Page(s) 435–446

Abstract: The adaptation of behavior and physiology to changes in the ambient light level is of crucial importance to life. These adaptations include the light modulation of neuroendocrine function and temporal alignment of physiology and behavior to the day:night ...

Abstract	The adaptation of behavior and physiology to changes in the ambient light level is of crucial importance to life. These adaptations include the light modulation of neuroendocrine function and temporal alignment of physiology and behavior to the day:night cycle by the circadian clock. These non-image-forming (NIF) responses can function independent of rod and cone photoreceptors but depend on ocular light reception, suggesting the participation of novel photoreceptors in the eye. The discovery of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) and genetic proof for its important role in major NIF responses have offered an exciting entry point to comprehend how mammals adapt to the light environment. Here, we review the recent advances in our understanding of the emerging roles of melanopsin and ipRGCs. These findings now offer new avenues to understand the role of ambient light in sleep, alertness, dependent physiologies and potential pharmacological intervention as well as lifestyle modifications to improve the quality of life.
MeSH term(s)	Adaptation, Physiological/radiation effects ; Animals ; Behavior/radiation effects ; Humans ; Light ; Retinal Ganglion Cells/cytology ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/radiation effects ; Rod Opsins/chemistry ; Rod Opsins/genetics ; Rod Opsins/metabolism ; Vision, Ocular/radiation effects
Chemical Substances	Rod Opsins ; melanopsin
Language	English
Publishing date	2010-08-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2010.07.005
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Zs.A 4345: Show issues

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Article ; Online: CRY links the circadian clock and CREB-mediated gluconeogenesis.

Hatori, Megumi / Panda, Satchidananda

Cell research

2010 Volume 20, Issue 12, Page(s) 1285–1288

MeSH term(s)	ARNTL Transcription Factors/metabolism ; Animals ; Blood Glucose/analysis ; CLOCK Proteins/metabolism ; Circadian Clocks ; Cryptochromes/genetics ; Cryptochromes/metabolism ; Cyclic AMP/metabolism ; Cyclic AMP Response Element-Binding Protein/genetics ; Cyclic AMP Response Element-Binding Protein/metabolism ; GTP-Binding Protein alpha Subunits, Gs/metabolism ; Gluconeogenesis ; Mice ; Period Circadian Proteins/genetics ; Period Circadian Proteins/metabolism ; Phosphorylation
Chemical Substances	ARNTL Transcription Factors ; Blood Glucose ; Cry1 protein, mouse ; Cry2 protein, mouse ; Cryptochromes ; Cyclic AMP Response Element-Binding Protein ; Per1 protein, mouse ; Per2 protein, mouse ; Period Circadian Proteins ; Cyclic AMP (E0399OZS9N) ; CLOCK Proteins (EC 2.3.1.48) ; Clock protein, mouse (EC 2.3.1.48) ; GTP-Binding Protein alpha Subunits, Gs (EC 3.6.5.1)
Language	English
Publishing date	2010-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/cr.2010.152
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Zs.A 5283: Show issues

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Article ; Online: Biosynthesis and biological actions of pineal neurosteroids in domestic birds.

Tsutsui, Kazuyoshi / Haraguchi, Shogo / Hatori, Megumi / Hirota, Tsuyoshi / Fukada, Yoshitaka

Neuroendocrinology

2013 Volume 98, Issue 2, Page(s) 97–105

Abstract: The central and peripheral nervous systems have the capacity of synthesizing steroids de novo from cholesterol, the so-called 'neurosteroids'. De novo synthesis of neurosteroids from cholesterol appears to be a conserved property across the subphylum ... ...

Abstract	The central and peripheral nervous systems have the capacity of synthesizing steroids de novo from cholesterol, the so-called 'neurosteroids'. De novo synthesis of neurosteroids from cholesterol appears to be a conserved property across the subphylum vertebrata. Until recently, it was generally believed that neurosteroids are produced in neurons and glial cells in the central and peripheral nervous systems. However, our recent studies on birds have demonstrated that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol. 7α-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity of juvenile birds, connecting light-induced gene expression with locomotion. The other major pineal neurosteroid allopregnanolone is involved in Purkinje cell survival by suppressing the activity of caspase-3, a crucial mediator of apoptosis during cerebellar development. This review is an updated summary of the biosynthesis and biological actions of pineal neurosteroids.
MeSH term(s)	Animals ; Animals, Domestic ; Birds/physiology ; Cell Survival/drug effects ; Coturnix ; Motor Activity/drug effects ; Neurotransmitter Agents/biosynthesis ; Neurotransmitter Agents/pharmacology ; Neurotransmitter Agents/physiology ; Pineal Gland/metabolism ; Purkinje Cells/drug effects ; Purkinje Cells/physiology
Chemical Substances	Neurotransmitter Agents
Language	English
Publishing date	2013
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	123303-8
ISSN	1423-0194 ; 0028-3835
ISSN (online)	1423-0194
ISSN	0028-3835
DOI	10.1159/000353782
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Zs.A 531: Show issues

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Article ; Online: Isoform-selective regulation of mammalian cryptochromes.

Miller, Simon / Son, You Lee / Aikawa, Yoshiki / Makino, Eri / Nagai, Yoshiko / Srivastava, Ashutosh / Oshima, Tsuyoshi / Sugiyama, Akiko / Hara, Aya / Abe, Kazuhiro / Hirata, Kunio / Oishi, Shinya / Hagihara, Shinya / Sato, Ayato / Tama, Florence / Itami, Kenichiro / Kay, Steve A / Hatori, Megumi / Hirota, Tsuyoshi

Nature chemical biology

2020 Volume 16, Issue 6, Page(s) 676–685

Abstract: CRY1 and CRY2 are essential components of the circadian clock controlling daily physiological rhythms. Accumulating evidences indicate distinct roles of these highly homologous proteins, in addition to redundant functions. Therefore, the development of ... ...

Abstract	CRY1 and CRY2 are essential components of the circadian clock controlling daily physiological rhythms. Accumulating evidences indicate distinct roles of these highly homologous proteins, in addition to redundant functions. Therefore, the development of isoform-selective compounds represents an effective approach towards understanding the similarities and differences of CRY1 and CRY2 by controlling each isoform individually. We conducted phenotypic screenings of circadian clock modulators, and identified KL101 and TH301 that selectively stabilize CRY1 and CRY2, respectively. Crystal structures of CRY-compound complexes revealed conservation of compound-binding sites between CRY1 and CRY2. We further discovered a unique mechanism underlying compound selectivity in which the disordered C-terminal region outside the pocket was required for the differential effects of KL101 and TH301 against CRY isoforms. By using these compounds, we found a new role of CRY1 and CRY2 as enhancers of brown adipocyte differentiation, providing the basis of CRY-mediated regulation of energy expenditure.
MeSH term(s)	Animals ; Binding Sites ; Circadian Clocks ; Cryptochromes/chemistry ; Cryptochromes/genetics ; Fibroblasts/metabolism ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Male ; Mice, Knockout ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Isoforms/chemistry ; Protein Isoforms/genetics ; Thermodynamics
Chemical Substances	CRY1 protein, human ; CRY2 protein, human ; Cryptochromes ; Protein Isoforms
Language	English
Publishing date	2020-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/s41589-020-0505-1
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Zs.A 6251: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 90: Show issues

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