N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs), including repeat RNAs, plays important roles in tuning the chromatin state and transcription, but the intrinsic mechanism remains unclear. Here, we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs), which highly depends on the m6A-binding ability. Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs, which recapitulates the transcriptome regulation by the LINE1 scaffold. Detailed analyses revealed that YTHDC1 recognizes m6A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1. Moreover, the establishment of H3K9me3 on 2C-related retrotransposons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells, which consequently increases the transcriptional activities. Our study reveals a role of m6A in regulating the RNA scaffold, providing a new model for the RNA-chromatin cross-talk.

No abstract

Summary A small subgroup of embryonic stem cells (ESCs) exhibit molecular features similar to those of two-cell embryos (2C). However, it remains elusive whether 2C-like cells and 2C embryos share similar epigenetic features. Here, we map the genome-wide profiles of histone H3K4me3 and H3K27me3 in 2C-like cells. We found that the majority of genes in 2C-like cells inherit their histone status from ESCs. Among the genes showing a switch in their histone methylation status during 2C-like transitions, only a small number acquire 2C-embryo epigenetic signatures. In contrast, broad H3K4me3 domains display extensive loss in 2C-like cells. Most of the differentially expressed genes display decreased H3K4me3 and H3K27me3 levels in 2C-like cells, whereas de novo H3K4me3 deposition is closely linked with the expression levels of upregulated 2C-specific genes. Taken together, our study reveals the unique epigenetic profiles of 2C-like cells, facilitating the further exploration of totipotency in the future.

With the development of active distribution networks (ADNs), more uncertainties need to be considered in distribution network planning (DNP), which increases the difficulties in scenario selection. Given this background, a multi-stage bi-level DNP model is proposed considering coordinated operation of distributed generation (DG), energy storage system (ESS) and controllable load (CL). In this model, a novel selection strategy for restricted operation scenarios based on the shadow price is proposed to reduce the complexity of scenario selection and ease the computational burden substantially in virtue of the decoupling of ADN operation and planning. A set consisting of restricted operation scenarios is simulated as an information feedback from operators to planners. The active distribution network planning (ADNP) model is aimed to minimize the total cost of feeder investments, ESS investments, and the additional operation costs caused by severely constrained network resources. The decision variables include the location and type selections of feeders, and the siting, power and capacity of ESSs at each stage of a given planning horizon. An extended IEEE 33-node distribution system and an actual 62-node distribution system in Zhejiang, China are serviced to verify the proposed model. The results show that the proposed ADNP model can effectively select out the restricted operation scenarios and achieve an optimal ADNP scheme by balancing non-network solutions and network solutions. INDEX TERMS Active distribution network planning, multistage planning, restricted operation scenarios, shadow price, bi-level programming. NOMENCLATURE A. INDICES AND SETS Ope s,n Operation cost of daily scenario s at stage n. C Inv n Annualized investment cost at stage n.

No abstract