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Dimitrov, S.

Publications and source records attributed to Dimitrov, S..

3 recordsLinked to original sources

Hunger and sleep recruit distinct brain systems to form spatial memory

By demonstrating that hunger consolidates spatial memory via a non-hippocampal mechanism that critically involves the retrosplenial cortex, we identify a mode of memory formation that is distinct from well-known hippocampus-dependent memory formation during sleep. Food-deprived rats encoded object locations and, during a subsequent 2-h consolidation phase, either received food and slept (Sleep-Fed) or stayed awake (Wake-Fed), or remained hungry and stayed awake (Wake-Hungry). At later retrieval testing, both Wake-Hungry and Sleep-Fed rats exhibited robust spatial memory, whereas Wake-Fed rats did not. Blocking neuropeptide-Y (NPY) signaling during the consolidation phase abolished hunger-consolidated memory. Unlike sleep-dependent consolidation, hunger-consolidated memory did not require the hippocampus during consolidation or retrieval, and not even during encoding. In contrast, inhibiting retrosplenial cortex during retrieval abolished hunger-consolidated memory but spared memory formed during sleep. Thus, recruitment of brain systems to form spatial memory is tuned to specific brain states, and fundamentally differs between sleep and hunger.

neuroscience↗

Differential Histone-DNA Interactions Dictate Nucleosome Recognition of the Pioneer Transcription Factor Sox

Pioneer transcription factors (PTFs) have the remarkable ability to directly bind to chromatin for stimulating vital cellular processes. In this work, we dissect the universal binding mode of Sox PTF by combining extensive molecular simulations and DNA footprinting techniques. As a result, we show that when Sox consensus DNA is located at the solvent-facing DNA strand, Sox binds to the compact nucleosome without imposing any significant conformational changes. We also reveal that the basespecific Sox:DNA interactions (base reading) and the Sox-induced DNA changes (shape reading) are concurrently required for the sequence-specific DNA recognition. Among different nucleosomal positions, such a specific reading mechanism is satisfied solely at superhelical location 2 (SHL2). While SHL2 acts transparently to Sox binding, SHL4 permits only shape reading, and SHL0 (dyad) allows no reading mechanism. These findings demonstrate for the first time that Sox-based nucleosome recognition is essentially guided by the distinct histone-DNA interactions, permitting varying degrees of DNA flexibility.

biophysics↗

H2A.Z is dispensable for both basal and activated transcription in post-mitotic mouse muscles

The histone variant H2A.Z is enriched in nucleosomes surrounding the transcription start site of active promoters, suggesting that it might be implicated in transcription. It is also required during mitosis. However, evidences obtained so far mainly rely on correlative evidences obtained in actively dividing cells. We have defined a paradigm in which cell cycle cannot interfere with H2A.Z transcriptional studies by developing an in vivo systems to invalidate H2A.Z in terminally differentiated post-mitotic muscle cells to dissociate its role during transcription from its role during mitosis. ChIP-seq, RNA-seq and ATAC-seq experiments performed on H2A.Z KO post-mitotic muscle cells show that this histone variant is neither required to maintain nor to activate transcription. Altogether, this study provides in vivo evidence that in the absence of mitosis H2A.Z is dispensable for transcription and that the enrichment of H2A.Z on active promoters is rather a marker than an actor of transcriptional activity.

cell biology↗