scholarly journals An essential role for MEF2C in the cortical response to loss of sleep in mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Theresa E Bjorness ◽  
Ashwinikumar Kulkarni ◽  
Volodymyr Rybalchenko ◽  
Ayako Suzuki ◽  
Catherine Bridges ◽  
...  
Keyword(s):  
Gene Expression ◽  
Slow Wave ◽  
Transcriptional Activity ◽  
Slow Wave Sleep ◽  
Sleep Loss ◽  
Wave Activity ◽  
Altered Gene Expression ◽  
Mepsc Frequency ◽  
Differential Gene ◽  
Altered Gene

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep-loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss in C57BL/6J mice. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.

scholarly journals An essential role for MEF2C in the cortical response to loss of sleep

2020 ◽  
Author(s):  
Theresa E. Bjorness ◽  
Ashwinikumar Kulkarni ◽  
Volodymer Rybalchenko ◽  
Ayako Suzuki ◽  
Catherine Bridges ◽  
...  
Keyword(s):  
Gene Expression ◽  
Slow Wave ◽  
Transcriptional Activity ◽  
Slow Wave Sleep ◽  
Sleep Loss ◽  
Wave Activity ◽  
Altered Gene Expression ◽  
Mepsc Frequency ◽  
Differential Gene ◽  
Altered Gene

AbstractNeuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.One Sentence SummaryMEF2C is critical to the response to sleep loss.

scholarly journals Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders

2016 ◽  
Vol 113 (16) ◽  
pp. 4434-4439 ◽  
Author(s):  
Aoi Wakabayashi ◽  
Jacob C. Ulirsch ◽  
Leif S. Ludwig ◽  
Claudia Fiorini ◽  
Makiko Yasuda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Activity ◽  
Regulatory Elements ◽  
Binding Motif ◽  
Targeted Disruption ◽  
Altered Gene Expression ◽  
Whole Exome ◽  
Altered Gene ◽  
Insight Into

Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptional cis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonical GATA1 binding motif completely abrogated binding of the cofactor TAL1, which binds to a separate motif. Having verified the functionality of these three GATA1 motifs, we demonstrate strong evolutionary conservation of GATA1 motifs in regulatory elements proximal to other genes implicated in erythroid disorders, and show that targeted disruption of such elements results in altered gene expression. By modeling transcription factor binding patterns, we show that multiple transcription factors are associated with erythroid gene expression, and have created predictive maps modeling putative disruptions of their binding sites at key regulatory elements. Our study provides insight into GATA1 transcriptional activity and may prove a useful resource for investigating the pathogenicity of noncoding variants in human erythroid disorders.

scholarly journals Gene expression profiling of pre-eclamptic placentae by RNA sequencing

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Tea Kaartokallio ◽  
◽  
Alejandra Cervera ◽  
Anjuska Kyllönen ◽  
Krista Laivuori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Function ◽  
Placental Development ◽  
Phenotypic Characteristics ◽  
Altered Gene Expression ◽  
Differential Gene ◽  
Altered Gene ◽  
Microarray Studies ◽  
Functional Analyses ◽  
Differently Expressed Genes

Abstract Pre-eclampsia is a common and complex pregnancy disorder that often involves impaired placental development. In order to identify altered gene expression in pre-eclamptic placenta, we sequenced placental transcriptomes of nine pre-eclamptic and nine healthy pregnant women in pools of three. The differential gene expression was tested both by including all the pools in the analysis and by excluding some of the pools based on phenotypic characteristics. From these analyses, we identified altogether 53 differently expressed genes, a subset of which was validated by qPCR in 20 cases and 19 controls. Furthermore, we conducted pathway and functional analyses which revealed disturbed vascular function and immunological balance in pre-eclamptic placenta. Some of the genes identified in our study have been reported by numerous microarray studies (BHLHE40, FSTL3, HK2, HTRA4, LEP, PVRL4, SASH1, SIGLEC6), but many have been implicated in only few studies or have not previously been linked to pre-eclampsia (ARMS2, BTNL9, CCSAP, DIO2, FER1L4, HPSE, LOC100129345, LYN, MYO7B, NCMAP, NDRG1, NRIP1, PLIN2, SBSPON, SERPINB9, SH3BP5, TET3, TPBG, ZNF175). Several of the molecules produced by these genes may have a role in the pathogenesis of pre-eclampsia and some could qualify as biomarkers for prediction or detection of this pregnancy complication.

Molecular and Microscopic Analysis of Altered Gene Expression in Transgenic and Gene Targeted Mice

1996 ◽  
Vol 54 ◽  
pp. 12-13
Author(s):  
W. K. Jones ◽  
J. Robbins
Keyword(s):  
Gene Expression ◽  
Pulmonary Veins ◽  
Microscopic Analysis ◽  
Mouse Tissue ◽  
Adult Heart ◽  
Heavy Chains ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Pulmonary Myocardium

Two myosin heavy chains (MyHC) are expressed in the mammalian heart and are differentially regulated during development. In the mouse, the α-MyHC is expressed constitutively in the atrium. At birth, the β-MyHC is downregulated and replaced by the α-MyHC, which is the sole cardiac MyHC isoform in the adult heart. We have employed transgenic and gene-targeting methodologies to study the regulation of cardiac MyHC gene expression and the functional and developmental consequences of altered α-MyHC expression in the mouse.We previously characterized an α-MyHC promoter capable of driving tissue-specific and developmentally correct expression of a CAT (chloramphenicol acetyltransferase) marker in the mouse. Tissue surveys detected a small amount of CAT activity in the lung (Fig. 1a). The results of in situ hybridization analyses indicated that the pattern of CAT transcript in the adult heart (Fig. 1b, top panel) is the same as that of α-MyHC (Fig. 1b, lower panel). The α-MyHC gene is expressed in a layer of cardiac muscle (pulmonary myocardium) associated with the pulmonary veins (Fig. 1c). These studies extend our understanding of α-MyHC expression and delimit a third cardiac compartment.

Polymorphism of the MTHFR Gene is Associated with Altered Gene Expression in Colorectal Cancer

Endoscopy ◽  
2004 ◽  
Vol 36 (05) ◽  
Author(s):  
K Collins ◽  
GA Doherty ◽  
MR Sweeney ◽  
SM Byrne ◽  
AA Aftab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mthfr Gene ◽  
Altered Gene Expression ◽  
Altered Gene

Beef steers with average dry matter intake and divergent average daily gain have altered gene expression in the jejunum

2017 ◽  
Vol 0 (0) ◽  
pp. 0
Author(s):  
A. P. Foote ◽  
B. N. Keel ◽  
C. M. Zarek ◽  
A. K. Lindholm-Perry
Keyword(s):  
Gene Expression ◽  
Dry Matter ◽  
Average Daily Gain ◽  
Dry Matter Intake ◽  
Beef Steers ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Daily Gain

scholarly journals Altered gene expression in Chironomus riparius (insecta) in response to tire rubber and polystyrene microplastics

2021 ◽  
pp. 117462
Author(s):  
Victor Carrasco-Navarro ◽  
Ana-Belén Muñiz González ◽  
Jouni Sorvari ◽  
Jose-Luis Martínez Guitarte
Keyword(s):  
Gene Expression ◽  
Chironomus Riparius ◽  
Tire Rubber ◽  
Altered Gene Expression ◽  
Altered Gene
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