KLF4 facilitates chromatin accessibility remodeling in porcine early embryos

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear.By employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos.Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts.Furthermore,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos.In addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this process.Taken together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.

m^(6)A-modified RNAs possess distinct poly(A)tails

N^(6)-methyladenosine(m^(6)A)has been found to be the most common type of post-transcriptional chemical modification in mammalian mRNAs and long non-coding RNAs(lncRNAs)(Dominissini et al.,2012;Meyer et al.,2012).In both mammals and yeast,RNA m^(6)A preferentially occurs in both gene coding regions and 3’untranslated regions(3’-UTRs),implicating its fundamental roles in every aspect of post-transcriptional regulation,including splicing,stability,and translation(Wang et al.,2014,2015;Zhao et al.,2014;Yang et al.,2018b).

Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat

Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore important to identify the optimal NSPC type.In our study,we compared the transcriptomes of human fetal brain-derived NSPCs(BNSPCs),spinal cord-derived NSPCs(SCNSPCs)and H9 embryonic stem-cell derived NSPCs(H9-NSPCs)in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo.In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types.In vivo,compared with BNSPCs and H9-NSPCs,SCNSPCs exhibited the best therapeutic effects;in fact,SCNSPCs facilitated electrophysiological and hindlimb functional recovery.This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair,which is of great clinical significance.

Visualization of in vivo cell-cell contact in the present and in the past

Cells are specialized to perform diverse functions to support the development and homeostasis of a multicellular organism.Cell-cell contact can mediate important communications between cells to coordinate cellular activities,which are essential in multiple biological processes to maintain tissue structure and function(Armingol et al.,2021).In vivo cell-cell contact remains largely unexplored.Recently,Zhang et al.(2022)report a comprehensive toolbox to label ongoing cell-cell contact or to trace the historical cell-cell contact in vivo.

Comprehensive analysis of mRNA poly(A)tails by PAIso-seq2

Dear Editor,Poly(A)tails are added to the 3’-end of most mRNAs(Colgan and Manley,1997;Yu and Kim,2020).The regulatory roles of poly(A)tails have long been underestimated due to technical difficulties in analyzing homopolymers(Chang et al.,2014;Subtelny et al.,2014).Several methods were recently developed to accurately measure their length(Chang et al.,2014;Legnini et al.,2019;Liu et al.,2019;Liu et al.

Comparative Analysis of JmjC Domain-containing Proteins Reveals the Potential Histone Demethylases in Arabidopsis and Rice

Histone methylation homeostasis is achieved by controlling the balance between methylation and demethylation to maintain chromatin function and developmental regulation. In animals, a conserved Jumonji C （JmjC） domain was found in a large group of histone demethylases. However, it is still unclear whether plants also contain the JmjC domain- containing active histone demethylases. Here we performed genome-wide screen and phylogenetic analysis of JmjC domain-containing proteins in the dicot plant, Arabidopsis, and monocot plant rice, and found 21 and 20 JmjC domain-containing, respectively. We also examined the expression of JmjC domain-containing proteins and compared them to human JmjC counterparts for potential enzymatic activity. The spatial expression patterns of the Arabidopsis JmjC domain-containing genes revealed that they are all actively transcribed genes. These active plant JmjC domain-containing genes could possibly function in epigenetic regulation to antagonize the activity of the large number of putative SET domain-containing histone methyltransferase activity to dynamically regulate histone methylation homeostasis.

Single-cell RNA sequencing reveals Nestin+active neural stem cells outside the central canal after spinal cord injury

Neural stem cells(NSCs)in the spinal cord hold great potential for repair after spinal cord injury(SCI).The ependyma in the central canal(CC)region has been considered as the NSCs source in the spinal cord.However,the ependyma function as NSCs after SCI is still under debate.We used Nestin as a marker to isolate potential NSCs and their immediate progeny,and characterized the cells before and after SCI by single-cell RNA-sequencing(scRNA-seq).We identified two subgroups of NSCs:the subgroup located within the CC cannot prime to active NSCs after SCI,while the subgroup located outside the CC were activated and exhibited the active NSCs properties after SCI.We demonstrated the comprehensive dynamic transcriptome of NSCs from quiescent to active NSCs after SCI.This study reveals that Nestin+cells outside CC were NSCs that activated upon SCI and may thus serve as endogenous NSCs for regenerative treatment of SCI in the future.

The enzymatic activity of Arabidopsis protein arginine methyltransferase 10 is essential for flowering time regulation

Arabidopsis AtPRMT10 is a plant-specific type I protein arginine methyltransferase that can asymmetrically dimethylate arginine 3 of histone H4 with auto-methylation activity.Mutations of AtPRMT10 derepress FLOWERING LOCUS C(FLC)expression resulting in a late-flowering phenotype.Here,to further investigate the biochemical characteristics of AtPRMT10,we analyzed a series of mutated forms of the AtPRMT10 protein.We demon-strate that the conserved“VLD”residues and“double-E loop”are essential for enzymatic activity of AtPRMT10.In addition,we show that Arg54 and Cys259 of AtPRMT10,two residues unreported in animals,are also important for its enzymatic activity.We find that Arg13 of AtPRMT10 is the auto-methylation site.However,substitution of Arg13 to Lys13 does not affect its enzymatic activity.In vivo complementation assays reveal that plants expressing AtPRMT10 with VLD-AAA,E143Q or E152Q mutations retain high levels of FLC expression and fail to rescue the late-flowering phenotype of atprmt10 plants.Taken together,we conclude that the methyltransferase activity of AtPRMT10 is essential for repressing FLC expression and promoting flowering in Arabidopsis.

H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination

DNA methylation and histone lysine tri-methylation at H3K27(H3K27me3)are two chromatin modifications for transcriptional gene silencing,which play important roles in diverse biological processes,including cell fate determination and cell lineage commitment.These two marks are largely mutually exclusive and target distinct sets of genes in the mammalian genome.However,how H3K27me3 shapes the DNA methylome remains elusive.Here,we report that the loss of H3K27me3 modification leads to increased DNA methylation at previously marked H3K27me3 sites,indicating that H3K27me3 negatively regulates DNA methylation.Genome-wide analysis of H3 ubiquitination,essential for recruitment and activation of DNA methyltransferase DNMT1,reveals the absence of H3 ubiquitination at H3K27me3 marked nucleosomes.Moreover,loss of H3K27me3 modification induces an increase in H3K18 ubiquitination at the corresponding hyper-methylated loci.Importantly,we show that H3K27me3 directly inhibits UHRF1-mediated H3 ubiquitination toward nucleosomes in a defined biochemical assay.Taken together,our findings reveal a general mechanism for H3K27me3-mediated shaping of the mammalian DNA methylome via modulation of H3 ubiquitination.

BAP60 plays an opposite role to the MRT-NURF complex in regulating lipid droplet size

The lipid droplet(LD)is a unique cellular organelle with a phospholipid monolayer coated with resident proteins.LDs are important for cellular neutral lipid storage and utilization.As spherical balls,LDs accommodate a lot more neutral lipids with a small increase of size.Disrupted LD dynamics,which can be reflected by abnormal LD size alteration,has been linked to many important metabolic diseases,including obesity,neutral lipid storage disease(NLSD).

Mapping Genome-wide Binding Sites of Prox1 in Mouse Cochlea Using the CUT&RUN Approach

Dear Editor,Our auditory organ,the cochlea,resides in the ventral portion of the inner ear,and its sensory epithelium,the organ of Corti,contains hair cells(HCs)and supporting cells(SCs),which are both descendants of the same progenitors.HCs are prone to damage by multiple ototoxic factors,and how to regenerate damaged HCs using key genes involving cochlear development is of importance[1,2].Cochlear progenitor cells express Sox2 and prolif-erate before embryonic day 12.5(E12.5)in the mouse but become quiescent in an apical-to-basal gradient between E12.5 and E14.5[3].

Drosophila Homolog of FMRP Maintains Genome Integrity by Interacting with Piwi

Fragile X syndrome （FraX）, the most common form of inherited mental retardation, is caused by the absence of the evolutionally conserved fragile X mental retardation protein （FMRP）. While neuronal functions of FMRP have been intensively studied for the last two decades, its role in non-neuronal cells remains poorly understood. Piwi, a key component of the Piwi-interacting RNA （piRNA） pathway, plays an essential role in germline development. In the present study, we report that similar to piwi, dfmrl, the Drosophila homolog of human FMR1, is required for transposon suppression in the germlines. Genetic analyses showed that dfmrl and piwi act synergistically in heterochromatic silencing, and in inhibiting the differentiation of primordial germline cells and transposon expression. Northern analyses showed that roo piRNA expression levels are reduced in dfmrl mutant ovaries, suggesting a role of dfmrl in piRNA biogenesis. Biochemical analysis demonstrated a physical interaction between dFMRP and Piwi via their N-termini. Taken together, we propose that dFMRP cooperates with Piwi in maintaining genome integrity by regulating heterochromatic silencing in somatic cells and suppressing transposon activity via the piRNA pathway in germlines.

The start of a human life program

The genetic information of a human being is encoded in the genomic DNA of about 3 billion base pairs.Every new individual starts from a one-cell zygote,or called fertilized egg,carrying genetic and epigenetic information from the parents.