Animals create implicit memories of the time of day that significant events occur then anticipate the recurrence of those conditions at the same time on subsequent days. We tested the hypothesis that implicit time memory for daily encounters relies on the setting of the canonical circadian clockwork in brain areas involved in the formation or expression of context memories. We conditioned mice to avoid locations paired with a mild foot shock at one of two Zeitgeber times set 8 hours apart. Place avoidance was exhibited only when testing time matched the prior training time. The suprachiasmatic nucleus, dorsal striatum, nucleus accumbens, cingulate cortex, hippocampal complex, and amygdala were assessed for clock gene expression. Baseline phase dependent differences in clock gene expression were found in most tissues. Evidence for conditioned resetting of a molecular circadian oscillation was found only in the striatum (dorsal striatum and nucleus accumbens shell), and specifically for Per2 expression. There was no evidence of glucocorticoid stress response in any tissue. The results are consistent with a model where temporal conditioning promotes a selective Per2 response in dopamine-targeted brain regions responsible for sensorimotor integration, without resetting the entire circadian clockwork.

• MeSH
• čas MeSH
• cirkadiánní hodiny * MeSH
• cirkadiánní proteiny Period biosyntéza   MeSH
• corpus striatum fyziologie   MeSH
• exprese genu * MeSH
• messenger RNA biosyntéza   MeSH
• modely neurologické MeSH
• myši inbrední C57BL MeSH
• podmiňování (psychologie) * MeSH
• stanovení celkové genové exprese MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Transdifferentiation of fibroblasts into induced neuronal cells (iNs) by the neuron-specific transcription factors Brn2, Myt1l, and Ascl1 is a paradigmatic example of inter-lineage conversion across epigenetically distant cells. Despite tremendous progress regarding the transcriptional hierarchy underlying transdifferentiation, the enablers of the concomitant epigenome resetting remain to be elucidated. Here, we investigated the role of KMT2A and KMT2B, two histone H3 lysine 4 methylases with cardinal roles in development, through individual and combined inactivation. We found that Kmt2b, whose human homolog's mutations cause dystonia, is selectively required for iN conversion through suppression of the alternative myocyte program and induction of neuronal maturation genes. The identification of KMT2B-vulnerable targets allowed us, in turn, to expose, in a cohort of 225 patients, 45 unique variants in 39 KMT2B targets, which represent promising candidates to dissect the molecular bases of dystonia.

• MeSH
• buněčná diferenciace genetika   MeSH
• dystonie genetika   MeSH
• embryo savčí cytologie   MeSH
• epigeneze genetická MeSH
• fibroblasty cytologie   MeSH
• genetické asociační studie * MeSH
• histonlysin-N-methyltransferasa metabolismus   MeSH
• histony metabolismus   MeSH
• lidé MeSH
• lysin metabolismus   MeSH
• metylace MeSH
• myši knockoutované MeSH
• neurony metabolismus   patologie   MeSH
• protoonkogenní protein MLL metabolismus   MeSH
• transdiferenciace buněk * genetika   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH