Pilocarpine-induced seizures associate with modifications of LSD1/CoREST/HDAC1/2 epigenetic complex and repressive chromatin in mice hippocampus

Noches, Verónica; Rivera, Carlos; González, Mauricio; Merello, Gianluca; Olivares-Costa, Montserrat; Andrés, Marı́a Estela

doi:10.1016/j.bbrep.2020.100889

Cited by 1 publication

(1 citation statement)

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“…And it has been reported the genes occupied by Rcor2 and LSD1 were with significantly reduced histone H3 lysine 4 (H3K4me1), which is linked to active transcription. In addition, pilocarpine-induced seizures are associated with increased protein levels of LSD1 and Rcor2 in accordance with increased H3 lysine 9 trimethylation (H3K9me3), which is generally associated with silenced genes [ 19 , 20 ]. Thus, we examined the protein level of H3K9me3 and H3K4me1 in Rcor2 −/− mESCs and WT mESCs, and our results showed a slight reduction of both H3K9me3 and H3K4me1 in Rcor2 −/− mESCs compared to WT mESCs ( Figure 5(a) ).…”

Section: Resultsmentioning

confidence: 99%

Rcor2 Is Required for Somatic Differentiation and Represses Germline Cell Fate

Pei

Zhang

et al. 2022

Stem Cells International

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Rcor2, the corepressor 2 of REST, a transcriptional repressor, is predominantly expressed in embryonic stem cells (ESCs) and plays a major role in regulating ESC pluripotency and neurogenesis. The function of Rcor2 in development of other germ layers is yet unclear. We utilized a Rcor2-/- mouse embryonic stem cell (mESC) line to investigate the role of Rcor2 in mESC differentiation. Rcor2-/- mESC shows reduced proliferation and severely compromised capacity to differentiate to all three germ layers. In contrast, Rcor2 knockout promotes primordial germ cells (PGCs) specific gene expression and possibly PGC formation. Mechanistically, we revealed that Rcor2 inhibits expression of genes required for PGC development, such as Dppa3 and Dazl, by associating to their promoters and enhancing local suppressive H3K9me3 modifications. Our results suggest that Rcor2 plays an important role in somatic cell fate determination by suppressing PGC differentiation through regulating epigenetic modifications of PGC specific genes.

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Section: Resultsmentioning

confidence: 99%