Rowley, S; Sun, X; Lima, I; Tavenier, A; Pinheiro de Oliveira, ACP; Dey, SK; Danzer, SC. Cannabinoid receptor 1/2 double-knockout mice develop epilepsy. Epilepsia. 2017; 58(12):e162-e166.
This study highlights the critical role of the endocannabinoid system in maintaining physiological activity of neuronal network. The deletion of both CB1 and CB2 receptors evoked spontaneous and handling-induced epilepsy in mice while deletion of either of the receptors was not sufficient. This work highlights the need to take into account that both CB receptors for developing drugs for preventing or inhibiting acquired seizures.
Maezawa, S; Yukawa, M; Alavattam, KG; Barski, A; Namekawa, SH. Dynamic reorganization of open chromatin underlies diverse transcriptomes during spermatogenesis. Nucleic Acids Research. 2018; 46(2):593-608.
During spermatogenesis, germ cells undergo massive cellular reconstruction and dynamic chromatin remodeling to facilitate highly diverse transcriptomes, required for the production of functional sperm. Our results unraveled the genome-wide, dynamic reorganization of open chromatin and reveal mechanisms that underlie diverse transcriptomes during spermatogenesis.
Sun, X; Tavenier, A; Deng, W; Leishman, E; Bradshaw, HB; Dey, SK. Metformin attenuates susceptibility to inflammation-induced preterm birth in mice with higher endocannabinoid levels. Biology of Reproduction. 2018; 98(2):208-217.
In pregnancy, higher endocannabinoids induce premature decidual senescence, which leads to preterm birth. Involved in premature decidual senescence are both mTOR and P38 signaling , and endocannabinoids activates P38 pathway. Previous studies showed that metformin ameliorates mTOR signaling induced premature decidual senescence. The current study showed that metformin also attenuates P38 induced premature senescence, which highlights the broad effects of metformin in preventing premature senescence.
Yue, M; Ogawa, Y. CRISPR/Cas9-mediated modulation of splicing efficiency reveals short splicing isoform of Xist RNA is sufficient to induce X-chromosome inactivation. Nucleic Acids Research. 2018; 46(5).
The CRISPR / Cas system derived from microbes is widely used as a tool to modify genomic DNA sequence. sing CRISPR / Cas-based splicing modulation, we investigate the short splicing isoform of Xist RNA. We find that the short Xist isoforms is sufficient to induce X- chromosome inactivation despite missing a large region from the long splicing Xist isoform.
Adams, SR; Maezawa, S; Alavattam, KG; Abe, H; Sakashita, A; Shroder, M; Broering, TJ; Rios, J; Thomas, MA; Lin, X; Price, CM; Barski, A; Andreassen, PR; Namekawa, SH. RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for escape gene activation on the sex chromosomes. PLoS Genetics. 2018; 14(2).
To produce unimpaired sperm, precise activation of germline-specific genes is an essential step during the late stages of spermatogenesis. We showed that RNF8 and SCML2 cooperate to regulate ubiquitination during meiosis, an early step to establish active histone modifications for subsequent gene activation.