Two zebrafish Notch-dependent hairy/Enhancer-of-split-related genes, her6 and her4, are required to maintain the coordination of cyclic gene expression in the presomitic mesoderm

Mammalian behavior and physiology undergo daily rhythms that are coordinated by an endogenous circadian timing system. This system has a hierarchical structure, in that a master pacemaker, residing in the suprachiasmatic nucleus of the ventral hypothalamus, synchronizes peripheral oscillators in virtually all body cells. While the basic molecular mechanisms generating the daily rhythms are similar in all cells, most clock outputs are cell-specific. This conclusion is based on genome-wide transcriptome profiling studies in several tissues that have revealed hundreds of rhythmically expressed genes. Cyclic gene expression in the various organs governs overt rhythms in behavior and physiology, encompassing sleep-wake cycles, metabolism, xenobiotic detoxification, and cellular proliferation. As a consequence, chronic perturbation of this temporal organization may lead to increased morbidity and reduced lifespan.

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Cellular Synchronisation through Unidirectional and Phase-Gated Signalling

10.1101/2020.11.26.399683 ◽

2020 ◽

Author(s):

Gregory Roth ◽

Georgios Misailidis ◽

Charisios D. Tsiairis

Keyword(s):

Gene Expression ◽

Notch Signalling ◽

The Other ◽

Cell Populations ◽

Coupling Mechanism ◽

Presomitic Mesoderm ◽

Unidirectional Coupling ◽

Alternative Framework ◽

Oscillatory Dynamics

AbstractMultiple natural and artificial oscillator systems achieve synchronisation when oscillators are coupled. The coupling mechanism, essentially the communication between oscillators, is often assumed to be continuous and bidirectional. However, the cells of the presomitic mesoderm synchronise their gene expression oscillations through Notch signalling, which is intermittent and directed from a ligand-presenting to a receptor-presenting cell. Motivated by this mode of communication we present a phase-gated and unidirectional coupling mechanism. We identify conditions under which it can successfully bring two or more oscillators to cycle in-phase. In the presomitic mesoderm we observed the oscillatory dynamics of two synchronizing cell populations and record one population halting its pace while the other keeps undisturbed, as would be predicted from our model. For the same system another important prediction, convergence to a specific range of phases upon synchronisation is also confirmed. Thus, the proposed mechanism accurately describes the coordinated oscillations of the presomitic mesoderm cells and provides an alternative framework for deciphering synchronisation.

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DETECTION AND DECOMPOSITION: TREATMENT-INDUCED CYCLIC GENE EXPRESSION DISRUPTION IN HIGH-THROUGHPUT TIME-SERIES DATASETS

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720012710023 ◽

2012 ◽

Vol 10 (06) ◽

pp. 1271002

Author(s):

YUHUA JIAO ◽

BRUCE A ROSA ◽

SOOKYUNG OH ◽

BERONDA L MONTGOMERY ◽

WENSHENG QIN ◽

...

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Periodic Pattern ◽

Gene Expression Patterns ◽

Detection Algorithms ◽

Knowledge Based ◽

Pattern Decomposition ◽

Cyclic Patterns ◽

Decomposition Treatment ◽

Cyclic Gene

Higher organisms possess many genes which cycle under normal conditions, to allow the organism to adapt to expected environmental conditions throughout the course of a day. However, treatment-induced disruption of regular cyclic gene expression patterns presents a significant challenge in novel gene discovery experiments because these disruptions can induce strong differential regulation events for genes that are not involved in an adaptive response to the treatment. To address this cycle disruption problem, we reviewed the state-of-art periodic pattern detection algorithms and a pattern decomposition algorithm (PRIISM), which is a knowledge-based Fourier analysis algorithm designed to distinguish the cyclic patterns from the rest gene expression patterns, and discussed potential future improvements.

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The Notch Pathway Intermediate HES-1 Silences CD4 Gene Expression

Molecular and Cellular Biology ◽

10.1128/mcb.18.12.7166 ◽

1998 ◽

Vol 18 (12) ◽

pp. 7166-7175 ◽

Cited By ~ 61

Author(s):

Han K. Kim ◽

Gerald Siu

Keyword(s):

Gene Expression ◽

T Cell ◽

Notch Signaling ◽

Signaling Pathway ◽

Transcriptional Control ◽

Notch Pathway ◽

Notch Signaling Pathway ◽

Thymic Development ◽

Enhancer Function ◽

Enhancer Of Split

ABSTRACT We have previously identified a transcriptional silencer that is critical for proper expression of the CD4 gene during T-cell development. Here we report that the Hairy/Enhancer of Split homologue HES-1, a transcription factor in the lin12/Notch signaling pathway, binds to an important functional site in the CD4 silencer. Overexpression of HES-1 leads to the silencer site-dependent repression of CD4 promoter and enhancer function as well as the downregulation of endogenous CD4 expression in CD4+ CD8−TH cells. Interestingly, overexpression of an activated form of Notch1 (NotchIC) leads to the repression of CD4 promoter and enhancer function both in the presence and absence of the silencer. NotchIC-mediated CD4 silencer function is not affected by the deletion of the HES-1-binding site, indicating that multiple factors binding to CD4 transcriptional control elements are responsive to signaling from this pathway, including other silencer-binding factors. Taken together, these data are consistent with the hypothesis that the lin12/Notch signaling pathway is important in thymic development and provide a molecular mechanism via the control of CD4 gene expression in which the lin12/Notch pathway affects T-cell developmental fate.

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