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Meiotic recombination is initiated by the formation of double-strand breaks (DSBs), which are repaired as either crossovers (COs) or noncrossovers (NCOs). In most mammals, PRDM9-mediated H3K4me3 controls the nonrandom distribution of DSBs; however, both the timing and mechanism of DSB fate control remain largely undetermined. Here, we generated comprehensive epigenomic profiles of synchronized mouse spermatogenic cells during meiotic prophase I, revealing spatiotemporal and functional relationships between epigenetic factors and meiotic recombination. We find that PRDM9-mediated H3K4me3 at DSB hotspots, coinciding with H3K27ac and H3K36me3, is intimately connected with the fate of the DSB. Our data suggest that the fate decision is likely made at the time of DSB formation: earlier formed DSBs occupy more open chromatins and are much more competent to proceed to a CO fate. Our work highlights an intrinsic connection between PRDM9-mediated H3K4me3 and the fate decision of DSBs, and provides new insight into the control of CO homeostasis.

Multiple pluripotent states have been described in mouse and human stem cells. Here, we apply single-cell RNA-seq to a newly established BMP4 induced mouse primed to naïve transition (BiPNT) system and show that the reset is not a direct reversal of cell fate but goes through a primordial germ cell-like cells (PGCLCs) state. We first show that epiblast stem cells bifurcate into c-Kit + naïve and c-Kit − trophoblast-like cells, among which, the naïve branch undergoes further transition through a PGCLCs intermediate capable of spermatogenesis in vivo. Mechanistically, we show that DOT1L inhibition permits the transition from primed pluripotency to PGCLCs in part by facilitating the loss of H3K79me2 from Gata3/6 . In addition, Prdm1 / Blimp1 is required for PGCLCs and naïve cells, while Gata2 inhibits PGC-like state by promoting trophoblast-like fate. Our work not only reveals an alternative route for primed to naïve transition, but also gains insight into germ cell development. Multiple pluripotent states have been described in mouse and human stem cells. Here the authors describe trajectories during BMP4 induced primed to naïve transition, which bifurcates into naïve and trophoblast-like branches with a PGC-like intermediate at the naïve branch.

Macrobenthic bioturbation affects the environment, and variances in habitat, such as decreased dissolved oxygen concentration and increased ammonia concentration, affects the macrobenthic community. The relationship between macrobenthos and habitat factors may be a mutually causal relationship. The bottom-sowing culture for Manila clam Ruditapes philippinarum in many coastal countries plays an important role in coastal fisheries, and the relationship between Manila clam and other macrobenthos affects the ecological stability of the bottom-sowing culture zone. It is necessary to explore the relationship between them to manage the waters used for the bottom-sowing culture for Manila clam. In this study , from June to October 2021, the field investigation on macrobenthos including Manila clam and their habitat factors, such as particle size, nutrient content, redox potential, and organic matter content, in 21 experimental communities enclosed by bolting-silk net in Shuangdao Bay, Weihai, Shandong, China was conducted, during which macrobenthos functional groups were determined by feed sources and motor behavior. The results showed that Manila clam biomass was 7.215±0.984 g/m2 (calculated by dry soft tissue weight), and it was positively correlated with the biomass of macrobebthos functional groups B1, G1 and P1; water content in sediment; sulfide content in interstitial water; the Shanon-Wiener diversity index; Pielou’s evenness index and the W statistic of the ABC (Abundance-Biomass Comparison) curve (p< 0.05). Moreover, it was negatively correlated with sediment particulate size and HCl-NO3 content in sediment (p< 0.05). The action of Manila clam to habitats was the dominant role of the interaction between clam and habitat. Thus, the bottom-sowing culture for Manila clam does not decrease the macrobenthic community stability, and the invasion of other macrobenthos into the bottom-sowing culture zones for Manila clam may be accidental or inevitable. The results of our study suggest that the management of the bottom-sowing culture for Manila clam should be conducted from ecosystem level; i.e., fishing and aquaculture in the same waters are regarded as two components of an ecosystem; manage them together, rather than treat them separately.

We apologize for an error introduced during format conversion in the paper published online on 18 October 2018. The resolution of the MALDI-TOF result in Fig. 1e underwent an unexpected reduction when transformed from Powerpoint format. The corrected Fig. 1e is provided below on the left.

The author would like to add the below information in this correction. A similar study from Chao Lu group was published online on 5 September 2019 in Nature, entitled “The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape” (Weinberg et al., 2019). Although both the studies reported the preferential recognition of H3K36me2 by DNMT3A PWWP, ours in addition uncovered a stimulation function by such interaction on the activity of DNMT3A. On the disease connections, we used a NSD2 gain-of-function model which led to the discovery of potential therapeutic implication of DNA inhibitors in the related cancers, while the other study only used NSD1 and DNMT3A loss-of-function models.

METTL3 (methyltransferase-like 3) mediates the N 6 -methyladenosine (m 6 A) methylation of mRNA, which affects the stability of mRNA and its translation into protein 1 . METTL3 also binds chromatin 2 – 4 , but the role of METTL3 and m 6 A methylation in chromatin is not fully understood. Here we show that METTL3 regulates mouse embryonic stem-cell heterochromatin, the integrity of which is critical for silencing retroviral elements and for mammalian development 5 . METTL3 predominantly localizes to the intracisternal A particle (IAP)-type family of endogenous retroviruses. Knockout of Mettl3 impairs the deposition of multiple heterochromatin marks onto METTL3-targeted IAPs, and upregulates IAP transcription, suggesting that METTL3 is important for the integrity of IAP heterochromatin. We provide further evidence that RNA transcripts derived from METTL3-bound IAPs are associated with chromatin and are m 6 A-methylated. These m 6 A-marked transcripts are bound by the m 6 A reader YTHDC1, which interacts with METTL3 and in turn promotes the association of METTL3 with chromatin. METTL3 also interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28, and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m 6 A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals. Binding of METTL3 to chromatin is enriched over IAP family endogenous retroviral elements in mouse embryonic stem cells, helping to ensure the integrity of heterochromatin at these elements.

RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While m 6 A has been widely studied, other RNA modifications, including 5 hmC, remain poorly characterised. We profiled m 6 A and 5 hmC epitranscriptomes, transcriptomes, translatomes and proteomes of monocytes and macrophages at rest and pro- and anti-inflammatory states. Transcriptome-wide mapping of m 6 A and 5 hmC reveals enrichment of m 6 A and/or 5 hmC on specific categories of transcripts essential for macrophage differentiation. Our analyses indicate that m 6 A and 5 hmC modifications are present in transcripts with critical functions in pro- and anti-inflammatory macrophages. Notably, we also discover the co-occurrence of m 6 A and 5 hmC on alternatively-spliced isoforms and/or opposing ends of the untranslated regions (UTR) of mRNAs with key roles in macrophage biology. In specific examples, RNA 5 hmC controls the decay of transcripts independently of m 6 A. This study provides (i) a comprehensive dataset to interrogate the role of RNA modifications in a plastic system (ii) a resource for exploring different layers of gene expression regulation in the context of human monocyte-to-macrophage differentiation and polarisation, (iii) new insights into RNA modifications as central regulators of effector cells in innate immunity.