Our journal club history from 2019

190116 NIFUJI
Molecular analysis of enthesopathy in a mouse model of hypophosphatemic rickets.
Development. 2018 Aug 10;145(15). pii: dev163519. doi: 10.1242/dev.163519.
X-linked hypophosphatemia (XLH) is characterized by impaired activation of vitamin D, elevated serum FGF23 levels and low serum phosphate levels, which impair bone mineralization. Paradoxically, an important complication of XLH is mineralization of the enthesis, which is accompanied with an expansion of Sox9-expressing cells, and enhanced BMP and IHH signaling. 

190213 NIFUJI
Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment
Nat Cell Biol.18, 2016
Mechanical force>> enrichment of emerin (Emd) at the bouter nuclear membrane >>the recruitment of non-muscle myosin IIA NMIIA to promote local actin polymerization  >> reduces nuclear actin levels >> attenuation of transcription and subsequent accumulation of H3K27me3 at facultative heterochromatin

190301 NIFUJI
Biomarkers for tissue engineering of the tendon-bone interface  PLos One, 2018 
An asymmetric distribution of enriched genes was observed in enthesis and cartilage transcriptome comparison suggesting that enthesis cells are more chondrocyte-like than tenocyte-like. Integrative analysis of transcriptome and proteome data identified ten enthesis biomarkers and six tendon biomarkers. 

190329 NIFUJI
Mechanically stimulated ATP release from murine bone cells is regulated by a
balance of injury and repair, eLife 2018;7

190408 NIFUJI
Compressive force induces reversible chromatin condensation and cell geometry–dependent transcriptional response, Mol BolCell 18

190508 NIFUJI
Nonuniformity in ligaments is a structural strategy for optimizing functionality, Olsen 9008–9013 ,PNAS 2018

190529 NIFUJI
Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres
Epigenetic Reprogramming from ES to muscle , Cell Reports 13
Cell Reports 3, 661–670, March 28, 2013
hESCs Are Resistant to MyoD-Mediated Myogenic Conversion
Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by in- structing MyoD positioning and allowing chromatin remodeling at target genes 

190617 Komatsu 
Cyclin D1 integrates G9a-mediated histone methylation. Oncogene, 2019  38:4232–4249 
 This study showed that cyclin D1 enhanced H3K9 dimethylation though direct association with G9a. Endogenous cyclin D1 was required for the recruitment of G9a to target genes in chromatin, for G9a- induced H3K9me2 of histones, and for NL-LAD interaction. Thus cyclin D1 is required for recruitment of G9a to target genes in chromatin and for H3K9 dimethylation. 

190708 Nifuji
Runx2 regulates cranial suture closure by inducing hedgehog, Fgf, Wnt and Pthlh signaling pathway gene expressions in suture mesenchymal cells 
Human Molecular Genetics, 2019, Vol. 28, No. 6 896–911 
Runx2-FGF-Gli-PTH-OB HumMolGen19

191021 Nifuji
Circuit Design Features of a Stable Two-Cell System
Zhou et al., 2018, Cell 172, 744–757
The macrophage-fibroblast cell circuit is stable and robust to perturbations. Cell- cell contact is essential for the stability of the macro- phage-fibroblast circuit. 

191112 IDENO  H3K9me3 Suv39h1 h2 Eset TKO
H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification 
Science 363, 294–297 (2019) 
High levels of compacted heterochromatin of H3K9me3 modification at protein-coding genes in early, uncommitted cells at the germ-layer stage, undergoing profound rearrangements and reduction upon differentiation with cell type–specific gene expression. Perturbation of the three H3K9me3-related methyltransferases revealed a pivotal role for H3K9me3 heterochromatin during lineage commitment at the onset of organogenesis and for lineage fidelity maintenance. 

Knockdown of formin mDia2 alters lamin B1 levels and increases osteogenesis in stem cells. STEM CELLS. 2019;1–16.
Does Nuclear structure / morphology affect cell determination?
+the main function of mDia2 is to enhance F-actin elongation
mDia 2KD in MSC
>> suppress lamin B1 levels , increase in A/C
>> changes nuclear morphology
>> promotes osteogenesis, suppress adipogenesis

200108 IDENO ChIL
A chromatin integration labelling method enables epigenomic profiling with lower input 
Nat Cell Biol 2019 Vol21 287-296 

They established an immunoprecipitation-free epigenomic profiling method named chromatin integration labelling (ChIL), which enables the amplification of genomic sequences closely associated with the target molecules before cell lysis. 

Genetic determinants and epigenetic effects of pioneer-factor occupancy. 
Nature Genetics, Vol 50 250, 2018; 250–258
Cofactor expression modulates FOXA2 enrichment at a subset of target sites. FOXA2 can occupy and change DNA accessibility without cell-cycle progression but requires replication to remove DNAme.

200210_KN_Excessive Cell Growth Causes Cytoplasm Dilution And
Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence
 Neurohr et al., 2019, Cell 176, 1083–1097
Optimal cell function requires maintenance of a narrow range of DNA:cytoplasm ratios and when cell size exceeds this ratio cytoplasmic dilution contributes to senescence 
Deviation from normal cell size interferes with cell function and proliferation 
DNA becomes limiting for cell function if cells grow too large
Uncoupling of protein synthesis and volume causes cytoplasm dilution in big cells 
Excessive cell growth contributes to functional decline in senescence 

200304 NIFUJI 
Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity 
Lateral Inhibition mechanical TAZ oocyte-Cell19
Xia et al., 2019, Cell 176, 1379–1392

Specification of a single precursor cell fate in zebrafish oogenesis is mediated by lateral inhibition driven by mechanical forces that lead to nuclear exclusion of a developmental transcriptional activator in neighboring cells. 
In the granulosa cells surrounding the developing zebrafish oocyte, increased levels of TAZ in the MPC drives cell growth, which is maintained through positive
feedback signaling via increased Integrin b1-ECM interactions. As the MPC increases in size, it elicits lateral inhibition in neighboring granulosa cells through
mechanical compression. Compression in neighboring cells reduces nuclear TAZ levels and inhibits these from adopting the MPC cell state.

200430 NIFUJI single cell embryos Chip Cell 19 
Profiling of Pluripotency Factors in Single Cells and Early Embryos 
Hainer et al., 2019, Cell 177, 1319–1329 
Chromatin binding by the pluripotency TF NANOG is highly dependent on the SWI/SNF chromatin remodeling complex in individual blastocysts 
only a fraction of TF binding sites is occupied in most cells 
>A modified CUT&RUN method allows chromatin profiling from small numbers of cells 
>Transcription factors are profiled from single cells and blastocyst-stage embryos 
>NANOG binding in vivo depends on SWI/SNF function 

Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage
Nava et al., 2020, Cell 181, 800–817
Stretch triggers amplitude-dependent supracellular and nuclear mechano responses. H3K9me3 heterochromatin mediates nuclear stiffness and membrane tension. Nuclear deformation-triggered Ca2+ alters chromatin rheology to prevent DNA damage. Supracellular alignment redistributes stress to restore chromatin state. 

200803 Ideno DNA methylome UHRF1 H3K9me
Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration.
Cell Research (2020) 0:1–17; 
The kinetics of replication-coupled maintenance are governed by the UHRF1–Ligase 1 and PCNA– DNMT1 interactions, whereas nucleosome occupancy and the interaction between UHRF1 and methylated H3K9 specifically regulate replication-uncoupled maintenance. 

200902 Nifuji Line1-ESC-Develop-Cell18
A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity 
Percharde et al., 2018, Cell 174, 391–405 
RNA transcribed from LINE1 elements acts as a nuclear scaffold to direct gene expression programs essential for ESC self-renewal and pre-implantation embryo development. 
LINE1 RNA is abundant and nuclear in mouse ESCs and pre- implantation embryos 
LINE1 knockdown inhibits ESC self-renewal and induces transition to a 2C state 
LINE1 RNA recruits Nucleolin/Kap1 to repress Dux and activate rRNA synthesis 
In embryos, LINE1 inhibition causes persistence of the 2C program and impairs ZGA 

200918 Nifuji ANKH-mechanical-ATP PosOnege20
The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP 
PLOS Genetics | https://doi.org/10.1371/journal.pgen.1008884  July 8, 2020 
ANKH provides a pathway for the release of nucleoside triphos- phates in general and, unexpectedly, the Krebs-cycle intermediate citrate. Mice lacking Ank activity (Ankank/ank mice), have substantially reduced concentrations of citrate in their plasma and urine. Citrate was even undetectable in urine of a human patient lacking functional ANKH. Bones of Ankank/ank mice have reduced mechanical strength and their bone matrix contains dramatically reduced levels of PPi and citrate. 

201118 Nifuji  RNA Promotes Open Chromatin Str CellChemBiol19
Neutralization of the Positive Charges on Histone Tails by RNA Promotes an Open Chromatin Structure 
Cell Chemical Biology 26, 1436–1449, October 17, 2019
>RNA regulates opening and closure of chromatin via charge
>RNA neutralizes histone tails and attenuates electrostatic compaction of chromatin
>Histones precipitate following removal of single-stranded RNA
>RNA facilitates formation of nucleosomes in vitro

210108 ANK-ENPP1 KO cementum-JDR20.pdf
Ablation of Pyrophosphate Regulators Promotes Periodontal Regeneration 
Journal of Dental Research,1–9,2020
Genetic ablation of Ank, Enpp1, or both factors increased cementum regeneration compared to controls at postoperative days (PODs) 15 and 30 associated with increased fluorochrome labeling and expression of mineralized tissue markers. dKO mice featured increased cementum thickness. No differences were noted in AB volume between genotypes, but osteoblast/osteocyte markers were increased in all KOs, partially mineralized osteoid volume was increased in dKO versus controls at POD15 , and mineral density was decreased 
210216 Nifuji
G9a Plays Distinct Roles in Maintaining DNA Methylation, Retrotransposon Silencing, and Chromatin Looping 
Cell Reports 33, 108315 October 27,2020
G9a functions through both catalytic- dependent and -independent mechanisms to repress regulatory elements and retrotransposons. Moreover, G9a affects chromatin looping by preventing aberrant CTCF/cohesin binding. 
Catalytic activity of G9a but not H3K9me2 functions in maintaining DNA methylation 
G9a regulates chromatin states and transcription through distinct mechanisms 
G9a maintains chromatin loops and TADs boundary strengths 
H3K9me2 prevents aberrant CTCF and cohesin binding, particularly at retrotransposons 

210310 Nifuji
Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization 
Nature genetics VOL 51 | SEPTEMBER 2019 | 1356–1368 
Megabase-sized topologically associating domains (TADs) can be in A (active) or B (inactive) subnuclear compartments, which exhibit early and late replication timing (RT), respectively. They show that A/B compartments change coordinately with RT changes genome wide during mouse embryonic stem cell (mESC) differentiation 

210531 NIFUJI
Gli1+ Periodontium Stem Cells Are Regulated by Osteocytes and Occlusal Force
Developmental Cell 54, 639–654, September 14, 2020   
Gli1+ cells as periodontal stem cells (PDLSCs). PDLSCs surround the neurovascular bundle and are regulated by osteocytes and biting force. 
Perivascular Gli1+ cells are stem cells (PDLSCs) for the periodontal tissue 
Wnt signal is essential for PDLSC activity
Sclerostin secreted from bones represses Wnt and PDLSC 
Biting force regulates PDLSC activity by modulating sclerostin level 

210721NIFUJI  H3K9me2-methyltransferase-3Dgenome-CommuBiol21
Regulation of mammalian 3D genome organization and histone H3K9 dimethylation by H3K9 methyltransferases 
H3K9me2 is regulated by all five MTases; G9a, GLP, SETDB1, SUV39H1, and SUV39H2. H3K9me2 and transcription in the A and B compartments are regulated by different MTases. H3K9me2 in the A compartments is primarily regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments is regulated by all five MTases. Furthermore, decreased H3K9me2 correlates with changes to more active compartmental state that accompanied transcriptional activation. 

211018 NIFUJI JDR19
Mechanoadaptive Responses in the Periodontium Are Coordinated by Wnt 
Journal of Dental Research 2019, Vol. 98(6) 689–697
They demonstrate the stress distributions within the periodontal ligament (PDL) caused by occlusal hyperloading. In direct response, a spatially restricted pattern of apoptosis is triggered in the stressed PDL, the temporal peak of which is coordinated with a spatially restricted burst in PDL cell proliferation. This turned to increased collagen deposition and a thicker, stiffer PDL that is adapted to its new hyperloading status. In the adjacent alveolar bone, hyperloading activates bone resorption, 
211027 Nifuji
Cells recognize osmotic stress through liquid–liquid phase separation lubricated with poly(ADP-ribose) 
Macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inacti- vation. A genome-wide small interfering RNA (siRNA) screen identifies an ASK3 inactivation regulator, nicotinamide phosphoribosyltransferase (NAMPT), related to poly(ADP-ribose) signaling. Poly(ADP-ribose) keeps ASK3 condensates in the liquid phase and enables ASK3 to become inactivated under hyperosmotic stress. 

211117 Nifuji 
MyoD induces ARTD1 nucleoplasmic poly-ADP-ribosylation fibroblast to MyoB 
MyoD induces ARTD1 and nucleoplasmic poly- ADP-ribosylation during fibroblast to myoblast transdifferentiation 
Bisceglie et al., iScience 24, 102432, May 21, 2021 
MyoD-dependent transdifferentiation of IMR90 to myoblasts induces ADP-ribosyltransferase ARTD1 expression 
Transdifferentiation induces nuclear ARTD1- dependent ADP- ribosylation in myoblasts 
ARTD1-mediated poly- ADP-ribosylation localizes to the nucleoplasm in myoblasts