Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function

Fogg, Paul C. M.; O’Neill, John S.; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma; McIntosh, Rebecca; Elliott, Christopher J.H.; Sweeney, Sean T.; Hastings, Michael H.; Chawla, Sangeeta

doi:10.1074/jbc.m114.606392

Cited by 38 publications

(31 citation statements)

References 32 publications

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“…MEF2 interactions with several of these molecules have already been established. In mammals, HDAC4 (histone deacetylase 4) is known to bind to MEF2 to repress transcription and Drosophila HDAC4 is important for muscle development, circadian rhythmicity and mushroom body function (Zhao et al, 2005;Fogg et al, 2014). An interaction between D-MEF2 and FAS2 (the fly ortholog of NCAM) in cell-cell communication or adhesion is suggested by our finding that D-mef2 hypomorphs exhibit an ectopic veination phenotype similar to that reported for fas2 loss of function mutant clones (Mao & Freeman, 2009).…”

Section: Mushroom Body Expression Pattern Of D-mef2supporting

confidence: 83%

Drosophila mef2is essential for normal mushroom body and wing development

Crittenden

Skoulakis

Goldstein

et al. 2018

Preprint

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MEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and muscle of insects and vertebrates and are essential for the differentiation of multiple cell types. We show that in the fruitfly Drosophila, MEF2 is essential for normal development of wing veins, and for mushroom body formation in the brain. In embryos mutant for D-mef2, there was a striking reduction in the number of mushroom body neurons and their axon bundles were not detectable. D-MEF2 expression coincided with the formation of embryonic mushroom bodies and, in larvae, expression onset was confirmed to be in post-mitotic neurons. With a D-mef2 point mutation that disrupts nuclear localization, we find that D-MEF2 is restricted to a subset of Kenyon cells that project to the α/β, and γ axonal lobes of the mushroom bodies, but not to those forming the α'/β' lobes. Our findings that ancestral mef2 is specifically important in dopamine-receptive neurons has broad implications for its function in mammalian neurocircuits.

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Section: Mushroom Body Expression Pattern Of D-mef2supporting

confidence: 83%

Drosophila mef2is essential for normal mushroom body and wing development

Crittenden

Skoulakis

Goldstein

et al. 2018

Preprint

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“…Histone acetylation is a specific type of histone PTM (i.e., one type of epigenetic mechanism) that is involved in numerous biological functions including circadian rhythms (Fogg et al, 2014;Malapeira et al, 2012), metabolism (Cosentino and Mostoslavsky, 2013;Kamemura et al, 2012;Katada et al, 2012;Karpac and Jasper, 2011;Chen et al, 2008), cellcycle regulation (Yamaguchi et al, 2010), and stress-response (Svetec et al, 2009;Matthias et al, 2008). This dynamic PTM mediates these diverse functions through coordinated, yet opposing, actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) which transcriptionally alter gene expression patterns by modifying chromatin structure to make specific sequences more (HATs) or less (HDACs) accessible to gene transcription machinery.…”

Section: Introductionmentioning

confidence: 99%

Changes in histone acetylation as potential mediators of pupal diapause in the flesh fly, Sarcophaga bullata

Reynolds

Bautista-Jimenez

Denlinger

2016

Insect Biochemistry and Molecular Biology

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The growing appreciation that epigenetic processes are integral to the responses of many organisms to changes in the environment suggests a possible role for epigenetics in coordination of insect diapause. The results we present suggest that histone modification may be one type of epigenetic process that contributes to regulation of pupal diapause in the flesh fly, Sarcophaga bullata. Reduction in total histone H3 acetylation in diapausing pupae, shifts in mRNA expression profiles of genes encoding histone acetyltransferase (HAT) and histone deacetylase (HDAC) in pre-diapause, diapause and post-diapause flies compared to their nondiapause counterparts, and alterations in HDAC enzyme activity during and post-diapause lend support to the hypothesis that this specific type of histone modification is involved in regulating diapause programming, maintenance, and termination. Transcription of genes encoding HDAC1, HDAC3, HDAC6, and Sirtuin2 were all upregulated in photosensitive first instar larvae programmed to enter pupal diapause, suggesting that histone deacetylation may be linked to the early decision to enter diapause. A 50% reduction in transcription of hdac3 and a corresponding 30% reduction in HDAC activity during diapause suggest that removal of acetyl groups from histones primarily occurs prior to diapause entry and that further histone deacetylation is not necessary to maintain diapause. Transcription of the HDAC genes was quickly elevated when diapause was terminated, followed by an increase in enzyme activity after a short delay. A maternal effect operating in these flies prevents pupal diapause in progeny whose mothers experienced pupal diapause, even if the progeny are reared in strong diapause-inducing short-day conditions. Such nondiapausing pupae had HDAC transcription profiles nearly identical to the profiles seen in nondiapausing pupae generated under a long-day photoperiod. Together, these results provide consistent evidence for histone acetylation and deacetylation as regulators of this insect's developmental trajectory.

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“…Conversely, if PDF signaling is dominant over NPF in a target neuron, cAMP levels would rise. It is not known whether cAMP regulates CLK activity, but cAMP does influence the activity of HDAC4, which is required for rhythmic per transcription (Fogg et al 2014). An increase in cAMP levels induces the phosphorylation and…”

Section: Other Neuropeptides and Evening Anticipationmentioning

confidence: 99%

“…Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a033589 nuclear entry of HDAC4, which promotes per expression at ZT16, with low cAMP levels and low per expression at ZT8 (Liu and Schneider 2013;Fogg et al 2014;Luan et al 2014). Expression of per remains low in flies expressing a nonfunctional form of HDAC4 (Fogg et al 2014). Assuming rhythmic bimodal dominance of either PDFR or NPFR1 GPCRs in s-LNvs, or simply the expression of one of the receptors in a given cluster, PER oscillations in a neuron can be regulated or reinforced by signals from other circadian neurons.…”

Section: Coordination Between Differentially Regulated Circadian Clocksmentioning

confidence: 99%

Coordination between Differentially Regulated Circadian Clocks Generates Rhythmic Behavior

Top

Young

2017

Cold Spring Harb Perspect Biol

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Specialized groups of neurons in the brain are key mediators of circadian rhythms, receiving daily environmental cues and communicating those signals to other tissues in the organism for entrainment and to organize circadian physiology. In Drosophila, the "circadian clock" is housed in seven neuronal clusters, which are defined by their expression of the main circadian proteins, Period, Timeless, Clock, and Cycle. These clusters are distributed across the fly brain and are thereby subject to the respective environments associated with their anatomical locations. While these core components are universally expressed in all neurons of the circadian network, additional regulatory proteins that act on these components are differentially expressed, giving rise to "local clocks" within the network that nonetheless converge to regulate coherent behavioral rhythms. In this review, we describe the communication between the neurons of the circadian network and the molecular differences within neurons of this network. We focus on differences in protein-expression patterns and discuss how such variation can impart functional differences in each local clock. Finally, we summarize our current understanding of how communication within the circadian network intersects with intracellular biochemical mechanisms to ultimately specify behavioral rhythms. We propose that additional efforts are required to identify regulatory mechanisms within each neuronal cluster to understand the molecular basis of circadian behavior. C ircadian rhythms are behavioral and physiological responses that allow anticipation of daily changes in the environment, such as day/ night cycles. Indeed, circadian rhythms are entrained by diurnal oscillations in light, temperature, and food availability, each of which can be considered a "zeitgeber," or "time giver." Such anticipatory behavior of daily events confers adaptive advantages on individuals that organize physiology around planetary rhythms, as well as within a species as a whole, for purposes of mating, cooperation, protection, etc. In a sense, rhythmic anticipation can be thought of as a primitive mechanism of planning and cognition.The circadian clock, consisting of transcriptional negative feedback loops, underlies the regulation of a ∼24-h behavioral rhythm. The molecular architecture of this feedback loop is conserved across the majority of multicellular organisms. In animals, the "master clock" is housed in specialized pacemaker neurons in the brain that coordinate various "peripheral clocks" throughout the organism to regulate daily physiological and behavioral changes.

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Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function

Cited by 38 publications

References 32 publications

Drosophila mef2is essential for normal mushroom body and wing development

Drosophila mef2is essential for normal mushroom body and wing development

Changes in histone acetylation as potential mediators of pupal diapause in the flesh fly, Sarcophaga bullata

Coordination between Differentially Regulated Circadian Clocks Generates Rhythmic Behavior

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