-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression
That not all histones are replaced by protamines in the sperm nucleus during spermiogenesis has been known for almost three decades, along with the notion that protamines do not bear any specific epigenetic information whereas histones typically carry posttranslational modifications with epigenetic regulatory functions. The enrichment of histones with distinct epigenetic modifications around transcriptional start sites, as well as unmethylated GC-rich promoter regions and exons in murine and human sperm, has recently been demonstrated by others at high resolution. The evolutionary conservation of the common principles underlying sperm histone retention provides a plausible rationale for epigenetic inheritance by nucleosomes. The present study takes a different approach towards testing the overarching hypothesis that sperm histones are linked to early embryonic gene expression by analyzing expression of genes in 2-cell embryos originating from sperm in which gene histone association of these genes was experimentally altered. The results are consistent with the aforementioned hypothesis and support the view of sperm histones as potential mediators of epigenetic inheritance through the male germ line, which could also contribute to phenotypic variation in mammals in response to environmental or dietary factors that affect sensitive chromatin-modulating pathways such as PAR metabolism.
Vyšlo v časopise: Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004317
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004317Souhrn
That not all histones are replaced by protamines in the sperm nucleus during spermiogenesis has been known for almost three decades, along with the notion that protamines do not bear any specific epigenetic information whereas histones typically carry posttranslational modifications with epigenetic regulatory functions. The enrichment of histones with distinct epigenetic modifications around transcriptional start sites, as well as unmethylated GC-rich promoter regions and exons in murine and human sperm, has recently been demonstrated by others at high resolution. The evolutionary conservation of the common principles underlying sperm histone retention provides a plausible rationale for epigenetic inheritance by nucleosomes. The present study takes a different approach towards testing the overarching hypothesis that sperm histones are linked to early embryonic gene expression by analyzing expression of genes in 2-cell embryos originating from sperm in which gene histone association of these genes was experimentally altered. The results are consistent with the aforementioned hypothesis and support the view of sperm histones as potential mediators of epigenetic inheritance through the male germ line, which could also contribute to phenotypic variation in mammals in response to environmental or dietary factors that affect sensitive chromatin-modulating pathways such as PAR metabolism.
Zdroje
1. RiveraRM (2010) Epigenetic aspects of fertilization and preimplantation development in mammals: lessons from the mouse. Syst Biol Reprod Med 56 : 388–404 doi:10.3109/19396368.2010.482726
2. BraunRE (2001) Packaging paternal chromosomes with protamine. Nat Genet 28 : 10–12 doi:10.1038/88194
3. BalhornR (2007) The protamine family of sperm nuclear proteins. Genome Biol 8 : 227 doi:10.1186/gb-2007-8-9-227
4. ArpanahiA, BrinkworthM, IlesD, KrawetzSA, ParadowskaA, et al. (2009) Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res 19 : 1338–1349 doi:10.1101/gr.094953.109
5. BrykczynskaU, HisanoM, ErkekS, RamosL, OakeleyEJ, et al. (2010) Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol 17 : 679–687 doi:10.1038/nsmb.1821
6. GatewoodJM, CookGR, BalhornR, BradburyEM, SchmidCW (1987) Sequence-specific packaging of DNA in human sperm chromatin. Science 236 : 962–964.
7. HammoudSS, PurwarJ, PfluegerC, CairnsBR, CarrellDT (2009) Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril 94 : 1728–33 doi:10.1016/j.fertnstert.2009.09.010
8. ZalenskayaIA, BradburyEM, ZalenskyAO (2000) Chromatin structure of telomere domain in human sperm. Biochem Biophys Res Commun 279 : 213–218 doi:10.1006/bbrc.2000.3917
9. PittoggiC, RenziL, ZaccagniniG, CiminiD, DegrassiF, et al. (1999) A fraction of mouse sperm chromatin is organized in nucleosomal hypersensitive domains enriched in retroposon DNA. J Cell Sci 112 (Pt 20) 3537–3548.
10. Gardiner-GardenM, BallesterosM, GordonM, TamPP (1998) Histone - and protamine-DNA association: conservation of different patterns within the beta-globin domain in human sperm. Mol Cell Biol 18 : 3350–3356.
11. KimminsS, Sassone-CorsiP (2005) Chromatin remodelling and epigenetic features of germ cells. Nature 434 : 583–589 doi:10.1038/nature03368
12. WykesSM, KrawetzSA (2003) The structural organization of sperm chromatin. J Biol Chem 278 : 29471–29477 doi:10.1074/jbc.M304545200
13. ErkekS, HisanoM, LiangC-Y, GillM, MurrR, et al. (2013) Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa. Nat Struct Mol Biol 20 : 1236 doi:10.1038/nsmb1013-1236b
14. Van der HeijdenGW, RamosL, BaartEB, van den BergIM, DerijckAA, et al. (2008) Sperm-derived histones contribute to zygotic chromatin in humans. BMC Dev Biol 8 : 34 doi:10.1186/1471-213X-8-34
15. Van der HeijdenGW, DerijckAA, RamosL, GieleM, van der VlagJ, et al. (2006) Transmission of modified nucleosomes from the mouse male germline to the zygote and subsequent remodeling of paternal chromatin. Dev Biol 298 : 458–469 doi:10.1016/j.ydbio.2006.06.051
16. BurtonA, Torres-PadillaME (2010) Epigenetic reprogramming and development: a unique heterochromatin organization in the preimplantation mouse embryo. Brief Funct Genomics 9 : 444–454 doi:10.1093/bfgp/elq027
17. FeilR (2009) Epigenetic asymmetry in the zygote and mammalian development. Int J Dev Biol 53 : 191–201 doi:10.1387/ijdb.082654rf
18. SantosF, PetersAH, OtteAP, ReikW, DeanW (2005) Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev Biol 280 : 225–236 doi:10.1016/j.ydbio.2005.01.025
19. MillerD, BrinkworthM, IlesD (2010) Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reprod Camb Engl 139 : 287–301 doi:10.1530/REP-09-0281
20. GatewoodJM, CookGR, BalhornR, SchmidCW, BradburyEM (1990) Isolation of four core histones from human sperm chromatin representing a minor subset of somatic histones. J Biol Chem 265 : 20662–20666.
21. NakamuraT, AraiY, UmeharaH, MasuharaM, KimuraT, et al. (2007) PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat Cell Biol 9 : 64–71 doi:10.1038/ncb1519
22. GuTP, GuoF, YangH, WuHP, XuGF, et al. (2011) The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477 : 606–610 doi:10.1038/nature10443
23. HajkovaP (2010) Epigenetic reprogramming–taking a lesson from the embryo. Curr Opin Cell Biol 22 : 342–350 doi:10.1016/j.ceb.2010.04.011
24. HalesBF, GrenierL, LalancetteC, RobaireB (2011) Epigenetic programming: from gametes to blastocyst. Birth Defects Res Clin Mol Teratol 91 : 652–665 doi:10.1002/bdra.20781
25. JohnsonGD, LalancetteC, LinnemannAK, LeducF, BoissonneaultG, et al. (2011) The sperm nucleus: chromatin, RNA, and the nuclear matrix. Reprod Camb Engl 141 : 21–36 doi:10.1530/REP-10-0322
26. Meyer-FiccaML, ScherthanH, BurkleA, MeyerRG (2005) Poly(ADP-ribosyl)ation during chromatin remodeling steps in rat spermiogenesis. Chromosoma 114 : 67–74 doi:10.1007/s00412-005-0344-6
27. Meyer-FiccaML, LoncharJD, IharaM, MeistrichML, AustinCA, et al. (2011) Poly(ADP-ribose) polymerases PARP1 and PARP2 modulate topoisomerase II beta (TOP2B) function during chromatin condensation in mouse spermiogenesis. Biol Reprod 84 : 900–909 doi:10.1095/biolreprod.110.090035
28. Meyer-FiccaML, LoncharJ, CredidioC, IharaM, LiY, et al. (2009) Disruption of Poly(ADP-Ribose) Homeostasis Affects Spermiogenesis and Sperm Chromatin Integrity in Mice. Biol Reprod 81 : 46–55 doi:10.1095/biolreprod.108.075390
29. Meyer-FiccaML, IharaM, LoncharJD, MeistrichML, AustinCA, et al. (2011) Poly(ADP-ribose) Metabolism Is Essential for Proper Nucleoprotein Exchange During Mouse Spermiogenesis. Biol Reprod 84 : 218–228 doi:10.1095/biolreprod.110.087361
30. BianchiPG, ManicardiGC, BizzaroD, BianchiU, SakkasD (1993) Effect of deoxyribonucleic acid protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa. Biol Reprod 49 : 1083–1088.
31. SaidaM, IlesD, ElnefatiA, BrinkworthM, MillerD (2011) Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin. Reprod Camb Engl 142 : 73–86 doi:10.1530/REP-10-0536
32. JohnsonWE, LiW, MeyerCA, GottardoR, CarrollJS, et al. (2006) Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A 103 : 12457–12462 doi:10.1073/pnas.0601180103
33. Meyer-FiccaML, LoncharJD, IharaM, BaderJJ, MeyerRG (2013) Alteration of poly(ADP-ribose) metabolism affects murine sperm nuclear architecture by impairing pericentric heterochromatin condensation. Chromosoma 122 : 319–335 doi:10.1007/s00412-013-0416-y
34. Huang daW, ShermanBT, LempickiRA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37 : 1–13 doi:10.1093/nar/gkn923
35. Huang daW, ShermanBT, LempickiRA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 : 44–57 doi:10.1038/nprot.2008.211
36. ZengF, BaldwinDA, SchultzRM (2004) Transcript profiling during preimplantation mouse development. Dev Biol 272 : 483–496 doi:10.1016/j.ydbio.2004.05.018
37. ZengF, SchultzRM (2005) RNA transcript profiling during zygotic gene activation in the preimplantation mouse embryo. Dev Biol 283 : 40–57 doi:10.1016/j.ydbio.2005.03.038
38. RousseauxS, KhochbinS (2012) Combined proteomic and in silico approaches to decipher post-meiotic male genome reprogramming in mice. Syst Biol Reprod Med 58 : 191–196 doi:10.3109/19396368.2012.663055
39. VavouriT, LehnerB (2011) Chromatin organization in sperm may be the major functional consequence of base composition variation in the human genome. PLoS Genet 7: e1002036 doi:10.1371/journal.pgen.1002036
40. MolaroA, HodgesE, FangF, SongQ, McCombieWR, et al. (2011) Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell 146 : 1029–1041 doi:10.1016/j.cell.2011.08.016
41. OlenderT, LancetD, NebertDW (2008) Update on the olfactory receptor (OR) gene superfamily. Hum Genomics 3 : 87–97.
42. SerizawaS, MiyamichiK, SakanoH (2004) One neuron-one receptor rule in the mouse olfactory system. Trends Genet TIG 20 : 648–653 doi:10.1016/j.tig.2004.09.006
43. SerizawaS, IshiiT, NakataniH, TsuboiA, NagawaF, et al. (2000) Mutually exclusive expression of odorant receptor transgenes. Nat Neurosci 3 : 687–693 doi:10.1038/76641
44. MalnicB, HironoJ, SatoT, BuckLB (1999) Combinatorial receptor codes for odors. Cell 96 : 713–723.
45. KrausWL (2008) Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation. Curr Opin Cell Biol 20 : 294–302 doi:10.1016/j.ceb.2008.03.006
46. TulinA, ChinenovY, SpradlingA (2003) Regulation of chromatin structure and gene activity by poly(ADP-ribose) polymerases. Curr Top Dev Biol 56 : 55–83.
47. LabergeRM, BoissonneaultG (2005) On the nature and origin of DNA strand breaks in elongating spermatids. Biol Reprod 73 : 289–296 doi:10.1095/biolreprod.104.036939
48. LisJT, KrausWL (2006) Promoter cleavage: a topoIIbeta and PARP-1 collaboration. Cell 125 : 1225–1227 doi:10.1016/j.cell.2006.06.016
49. YamauchiY, ShamanJA, WardWS (2010) Non-genetic contributions of the sperm nucleus to embryonic development. Asian J Androl doi:10.1038/aja.2010.75
50. FrizzellKM, GambleMJ, BerrocalJG, ZhangT, KrishnakumarR, et al. (2009) Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells. J Biol Chem 284 : 33926–33938 doi:10.1074/jbc.M109.023879
51. Le MayN, IltisI, AméJ-C, ZhovmerA, BiardD, et al. (2012) Poly (ADP-ribose) glycohydrolase regulates retinoic acid receptor-mediated gene expression. Mol Cell 48 : 785–798 doi:10.1016/j.molcel.2012.09.021
52. CortesU, TongWM, CoyleDL, Meyer-FiccaML, MeyerRG, et al. (2004) Depletion of the 110-kilodalton isoform of poly(ADP-ribose) glycohydrolase increases sensitivity to genotoxic and endotoxic stress in mice. Mol Cell Biol 24 : 7163–7178 doi:10.1128/MCB.24.16.7163-7178.2004
53. KrishnakumarR, KrausWL (2010) PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Mol Cell 39 : 736–749 doi:10.1016/j.molcel.2010.08.014
54. CaiafaP, ZlatanovaJ (2009) CCCTC-binding factor meets poly(ADP-ribose) polymerase-1. J Cell Physiol 219 : 265–70 doi:10.1002/jcp.21691
55. FarrarD, RaiS, ChernukhinI, JagodicM, ItoY, et al. (2010) Mutational analysis of the poly(ADP-ribosyl)ation sites of the transcription factor CTCF provides an insight into the mechanism of its regulation by poly(ADP-ribosyl)ation. Mol Cell Biol 30 : 1199–1216 doi:10.1128/MCB.00827-09
56. LuoX, KrausWL (2012) On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev 26 : 417–432 doi:10.1101/gad.183509.111
57. CaroneBR, FauquierL, HabibN, SheaJM, HartCE, et al. (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143 : 1084–1096 doi:10.1016/j.cell.2010.12.008
58. NgSF, LinRC, LaybuttDR, BarresR, OwensJA, et al. (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467 : 963–966 doi:10.1038/nature09491
59. LindemanLC, AndersenIS, ReinerAH, LiN, AanesH, et al. (2011) Prepatterning of Developmental Gene Expression by Modified Histones before Zygotic Genome Activation. Dev Cell 21 : 993–1004 doi:10.1016/j.devcel.2011.10.008
60. GrantGR, FarkasMH, PizarroAD, LahensNF, SchugJ, et al. (2011) Comparative analysis of RNA-Seq alignment algorithms and the RNA-Seq unified mapper (RUM). Bioinforma Oxf Engl 27 : 2518–2528 doi:10.1093/bioinformatics/btr427
61. AndersS, HuberW (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106 doi:10.1186/gb-2010-11-10-r106
62. NazarovIB, ShlyakhtenkoLS, LyubchenkoYL, ZalenskayaIA, ZalenskyAO (2008) Sperm chromatin released by nucleases. Syst Biol Reprod Med 54 : 37–46 doi:10.1080/19396360701876849
63. OliverosJC (2007) VENNY. An interactive tool for comparing lists with Venn Diagrams http://bioinfogp.cnb.csic.es/tools/venny/index.html.
Štítky
Genetika Reprodukčná medicína
Článek Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin PathwayČlánek Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human DiseasesČlánek G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify LongevityČlánek PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial MatrixČlánek Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus ConflictsČlánek The Impact of Population Demography and Selection on the Genetic Architecture of Complex TraitsČlánek Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar AcidificationČlánek The Case for Junk DNA
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 5- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- Genetic Interactions Involving Five or More Genes Contribute to a Complex Trait in Yeast
- A Mutation in the Gene in Dogs with Hereditary Footpad Hyperkeratosis (HFH)
- Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling
- Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution
- Genome-Wide Nucleosome Positioning Is Orchestrated by Genomic Regions Associated with DNase I Hypersensitivity in Rice
- Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy
- Single Nucleotide Variants in Transcription Factors Associate More Tightly with Phenotype than with Gene Expression
- Ribosomal Protein Mutations Induce Autophagy through S6 Kinase Inhibition of the Insulin Pathway
- Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases
- Epistatically Interacting Substitutions Are Enriched during Adaptive Protein Evolution
- Meiotic Drive Impacts Expression and Evolution of X-Linked Genes in Stalk-Eyed Flies
- G×G×E for Lifespan in : Mitochondrial, Nuclear, and Dietary Interactions that Modify Longevity
- Population Genomic Analysis of Ancient and Modern Genomes Yields New Insights into the Genetic Ancestry of the Tyrolean Iceman and the Genetic Structure of Europe
- p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision
- Whole Exome Re-Sequencing Implicates and Cilia Structure and Function in Resistance to Smoking Related Airflow Obstruction
- Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues
- R-loops Associated with Triplet Repeat Expansions Promote Gene Silencing in Friedreich Ataxia and Fragile X Syndrome
- PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix
- The Impairment of MAGMAS Function in Human Is Responsible for a Severe Skeletal Dysplasia
- Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Males
- Mlh2 Is an Accessory Factor for DNA Mismatch Repair in
- Activating Transcription Factor 6 Is Necessary and Sufficient for Alcoholic Fatty Liver Disease in Zebrafish
- The Spatiotemporal Program of DNA Replication Is Associated with Specific Combinations of Chromatin Marks in Human Cells
- Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts
- Genome-Wide Inference of Ancestral Recombination Graphs
- Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in
- SHP2 Regulates Chondrocyte Terminal Differentiation, Growth Plate Architecture and Skeletal Cell Fates
- The Impact of Population Demography and Selection on the Genetic Architecture of Complex Traits
- Retinoid-X-Receptors (α/β) in Melanocytes Modulate Innate Immune Responses and Differentially Regulate Cell Survival following UV Irradiation
- Genetic Dissection of the Female Head Transcriptome Reveals Widespread Allelic Heterogeneity
- Genome Sequencing and Comparative Genomics of the Broad Host-Range Pathogen AG8
- Copy Number Variation Is a Fundamental Aspect of the Placental Genome
- GOLPH3 Is Essential for Contractile Ring Formation and Rab11 Localization to the Cleavage Site during Cytokinesis in
- Hox Transcription Factors Access the RNA Polymerase II Machinery through Direct Homeodomain Binding to a Conserved Motif of Mediator Subunit Med19
- Drosha Promotes Splicing of a Pre-microRNA-like Alternative Exon
- Predicting the Minimal Translation Apparatus: Lessons from the Reductive Evolution of
- PAX6 Regulates Melanogenesis in the Retinal Pigmented Epithelium through Feed-Forward Regulatory Interactions with MITF
- Enhanced Interaction between Pseudokinase and Kinase Domains in Gcn2 stimulates eIF2α Phosphorylation in Starved Cells
- A HECT Ubiquitin-Protein Ligase as a Novel Candidate Gene for Altered Quinine and Quinidine Responses in
- dGTP Starvation in Provides New Insights into the Thymineless-Death Phenomenon
- Phosphorylation Modulates Clearance of Alpha-Synuclein Inclusions in a Yeast Model of Parkinson's Disease
- RPM-1 Uses Both Ubiquitin Ligase and Phosphatase-Based Mechanisms to Regulate DLK-1 during Neuronal Development
- More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta
- More of a Good Thing or Less of a Bad Thing: Gene Copy Number Variation in Polyploid Cells of the Placenta
- Heritable Transmission of Stress Resistance by High Dietary Glucose in
- Revertant Mutation Releases Confined Lethal Mutation, Opening Pandora's Box: A Novel Genetic Pathogenesis
- Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification
- A Genome-Wide Assessment of the Role of Untagged Copy Number Variants in Type 1 Diabetes
- Selectivity in Genetic Association with Sub-classified Migraine in Women
- A Lack of Parasitic Reduction in the Obligate Parasitic Green Alga
- The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast
- Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma
- Six Homeoproteins and a linc-RNA at the Fast MYH Locus Lock Fast Myofiber Terminal Phenotype
- EDR1 Physically Interacts with MKK4/MKK5 and Negatively Regulates a MAP Kinase Cascade to Modulate Plant Innate Immunity
- Genes That Bias Mendelian Segregation
- The Case for Junk DNA
- An In Vivo EGF Receptor Localization Screen in Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling
- Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder
- Hyperactivated Wnt Signaling Induces Synthetic Lethal Interaction with Rb Inactivation by Elevating TORC1 Activities
- Mutations in the Cholesterol Transporter Gene Are Associated with Excessive Hair Overgrowth
- Scribble Modulates the MAPK/Fra1 Pathway to Disrupt Luminal and Ductal Integrity and Suppress Tumour Formation in the Mammary Gland
- A Novel CH Transcription Factor that Regulates Expression Interdependently with GliZ in
- Phosphorylation of a WRKY Transcription Factor by MAPKs Is Required for Pollen Development and Function in
- Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics
- Spermatid Cyst Polarization in Depends upon and the CPEB Family Translational Regulator
- Insights into the Genetic Structure and Diversity of 38 South Asian Indians from Deep Whole-Genome Sequencing
- Intron Retention in the 5′UTR of the Novel ZIF2 Transporter Enhances Translation to Promote Zinc Tolerance in
- A Dominant-Negative Mutation of Mouse Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation
- Biased, Non-equivalent Gene-Proximal and -Distal Binding Motifs of Orphan Nuclear Receptor TR4 in Primary Human Erythroid Cells
- Ras-Mediated Deregulation of the Circadian Clock in Cancer
- Retinoic Acid-Related Orphan Receptor γ (RORγ): A Novel Participant in the Diurnal Regulation of Hepatic Gluconeogenesis and Insulin Sensitivity
- Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions
- Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2
- Paternal Poly (ADP-ribose) Metabolism Modulates Retention of Inheritable Sperm Histones and Early Embryonic Gene Expression
- Allele-Specific Genome-wide Profiling in Human Primary Erythroblasts Reveal Replication Program Organization
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix
- Null Mutation in PGAP1 Impairing Gpi-Anchor Maturation in Patients with Intellectual Disability and Encephalopathy
- Phosphorylation of a WRKY Transcription Factor by MAPKs Is Required for Pollen Development and Function in
- p53 Requires the Stress Sensor USF1 to Direct Appropriate Cell Fate Decision
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy