Novel transcriptional networks regulated by CLOCK in human neurons

Fontenot, Miles R.; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon C.; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A.; Takahashi, Joseph S.; Konopka, Genevieve

doi:10.1101/gad.305813.117

Cited by 32 publications

(32 citation statements)

References 106 publications

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“…Surprisingly, our comparative assessment of the temporal expression of circadian genes in eye/retina of zebrafish, mouse and baboon revealed a previously unknown difference. Circadian genes in zebrafish (Huang et al 2018) and mouse eye (Storch et al 2007)show rhythmic expression, while all key circadian genes were arrhythmic in baboon retina (Mure et al 2018) Similar non-circadian expression of Clock gene-a key circadian transcription factor was documented in human neurons and cortex (Fontenot et al 2017;Chen et al 2016). These differences hint towards an organ/organism-specific repurposing of core circadian genes whose biological significance is yet to be studied.…”

Section: Discussionmentioning

confidence: 84%

Identification of novel circadian transcripts in the zebrafish retina

Ramasamy

Sharma

Iyengar

et al. 2018

Preprint

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High fecundity, transparent embryos for monitoring the rapid development of organs and the availability of a well-annotated genome has made zebrafish a model organism of choice for developmental biology and neurobiology. This vertebrate model, a favourite in chronobiology studies, shows striking circadian rhythmicity in behaviour. Here, we identify novel genes in the zebrafish genome, which shows their expression in the zebrafish retina.We further resolve the expression pattern over time and assign specific novel transcripts to the retinal cell type, predominantly in the inner nuclear layer. Using chemical ablation and free run experiments we segregate the transcripts that are rhythmic when entrained by light from those that show sustained oscillations in the absence of external cues. The transcripts reported here with rigorous annotation and specific functions in circadian biology provide the groundwork for functional characterisation of novel players in the zebrafish retinal clock.

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Section: Discussionmentioning

confidence: 84%

Identification of novel circadian transcripts in the zebrafish retina

Ramasamy

Sharma

Iyengar

et al. 2018

Preprint

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“…Enrichment of CREB binding motif in module M1 gene promoters is consistent with its well-documented role in synaptic activitydependent gene regulation and neural plasticity 62,63 . Enrichment of NF-κB 64 , STAT3 65 and CLOCK 66 binding motifs in the module M1 gene promoters is interesting, too, as it suggests potential roles for additional extrinsic signaling pathways, i.e. stress, interferon, circadian rhythm, respectively, in the regulation of gene expression in neurons.…”

Section: Resultsmentioning

confidence: 99%

An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

Preissl

Hou

et al. 2020

Preprint

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25The mammalian cerebrum performs high level sensory, motor control and cognitive 26 functions through highly specialized cortical networks and subcortical nuclei. Recent 27 surveys of mouse and human brains with single cell transcriptomics 1-3 and high-28 throughput imaging technologies 4,5 have uncovered hundreds of neuronal cell types and 29 a variety of non-neuronal cell types distributed in different brain regions, but the cell-type-30 specific transcriptional regulatory programs responsible for the unique identity and 31 function of each brain cell type have yet to be elucidated. Here, we probe the accessible 32 chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse 33 isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to 34 define 491,818 candidate cis regulatory DNA elements in 160 distinct sub-types. We link 35 a significant fraction of them to putative target genes expressed in diverse cerebral cell 36 types and uncover transcriptional regulators involved in a broad spectrum of molecular 37 and cellular pathways in different neuronal and glial cell populations. Our results provide 38 a foundation for comprehensive analysis of gene regulatory programs of the mammalian 39 brain and assist in the interpretation of non-coding risk variants associated with various 40 neurological disease and traits in humans. To facilitate the dissemination of information, 41 we have set up a web portal (http://catlas.org/mousebrain).42 45 functions such as sensory processing, motor control, emotion, and cognition 6 . It is divided 46 into two hemispheres, each consisting of the cerebral cortex and various cerebral nuclei. 47The cerebral cortex is further divided into isocortex and allocortex. Isocortex, 48 characterized by six cortical layers, is a phylogenetically more recent structure that has 49 further expanded greatly in primates. It is responsible for sensory motor integration, 50 decision making, volitional motor command and reasoning. The allocortex, by contrast, is 51 phylogenetically the older structure that features three or four cortical layers. It includes 52 the olfactory bulb responsible for processing the sense of smell and the hippocampus 53 involved in learning, memory and spatial navigation. 54 55 The cerebral cortex and basal ganglia are made up of a vast number of neurons and glial 56 cells. The neurons can be classified into different types of excitatory projection neurons 57 and inhibitory interneurons, defined by the neural transmitters they produce and their 58 connective patterns with other neurons 7-9 . Understanding how the identity and function of 59 each brain cell type is established during development and modified by experience is one 60 of the fundamental challenges in brain research. Recent single cell RNA-seq and high 61 throughput imaging experiments have produced detailed cell atlases for both mouse and 62human brains 3-5,10-15 , leading to a comprehensive view of gene expression patterns in 63 different brain regions, c...

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“…Cross-species comparisons have also revealed CLOCK as a hub unique to transcription networks in the human frontal lobe that are related to brain development, human language emergence, and neuropsychiatric disease. Furthermore, in cell-based studies, CLOCK was found to coordinate neuronal migration, consistent with a role in early development, transcription network complexity, and diverse aging pathologies (Babbitt et al 2010;Konopka et al 2012;Fontenot et al 2017). Human brain development and transcriptional networks are also tightly coupled with splicing, which generates an additional level of neuronal diversity (Fogel et al 2012).…”

Section: Circadian Regulation Of Neuronal Activity-dependent Transcrimentioning

confidence: 72%

Neurogenetic basis for circadian regulation of metabolism by the hypothalamus

2019

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Circadian rhythms are driven by a transcription-translation feedback loop that separates anabolic and catabolic processes across the Earth's 24-h light-dark cycle. Central pacemaker neurons that perceive light entrain a distributed clock network and are closely juxtaposed with hypothalamic neurons involved in regulation of sleep/wake and fast/feeding states. Gaps remain in identifying how pacemaker and extrapacemaker neurons communicate with energy-sensing neurons and the distinct role of circuit interactions versus transcriptionally driven cellautonomous clocks in the timing of organismal bioenergetics. In this review, we discuss the reciprocal relationship through which the central clock drives appetitive behavior and metabolic homeostasis and the pathways through which nutrient state and sleep/wake behavior affect central clock function. Molecular dynamics of the circadian clock[

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Novel transcriptional networks regulated by CLOCK in human neurons

Cited by 32 publications

References 106 publications

Identification of novel circadian transcripts in the zebrafish retina

Identification of novel circadian transcripts in the zebrafish retina

An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

Neurogenetic basis for circadian regulation of metabolism by the hypothalamus

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