The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors
Publication Date
March 10, 2015
Journal
PLOS Genetics
Authors
Linya You, Kezhi Yan, Jinfeng Zhou, Hong Zhao, et al
Volume
11
Issue
3
Pages
e1005034
DOI
https://dx.plos.org/10.1371/journal.pgen.1005034
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1005034
Web of Science
000352197100026
Scopus
84926150217
Mendeley
http://www.mendeley.com/research/lysine-acetyltransferase-activator-brpf1-governs-dentate-gyrus-development-through-neural-stem-cells
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Mendeley | Further Information

{"title"=>"The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors", "type"=>"journal", "authors"=>[{"first_name"=>"Linya", "last_name"=>"You", "scopus_author_id"=>"55236554300"}, {"first_name"=>"Kezhi", "last_name"=>"Yan", "scopus_author_id"=>"54796364800"}, {"first_name"=>"Jinfeng", "last_name"=>"Zhou", "scopus_author_id"=>"57191733111"}, {"first_name"=>"Hong", "last_name"=>"Zhao", "scopus_author_id"=>"56175305800"}, {"first_name"=>"Nicholas R.", "last_name"=>"Bertos", "scopus_author_id"=>"57192120470"}, {"first_name"=>"Morag", "last_name"=>"Park", "scopus_author_id"=>"7404490591"}, {"first_name"=>"Edwin", "last_name"=>"Wang", "scopus_author_id"=>"15023495100"}, {"first_name"=>"Xiang Jiao", "last_name"=>"Yang", "scopus_author_id"=>"7406500524"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537404", "pui"=>"603514015", "doi"=>"10.1371/journal.pgen.1005034", "sgr"=>"84926150217", "scopus"=>"2-s2.0-84926150217", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"25757017"}, "id"=>"77db688a-cf00-3397-afe2-eddc4a822dd4", "abstract"=>"Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.", "link"=>"http://www.mendeley.com/research/lysine-acetyltransferase-activator-brpf1-governs-dentate-gyrus-development-through-neural-stem-cells", "reader_count"=>35, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>5, "Professor"=>1, "Professor > Associate Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>2, "Student > Bachelor"=>5, "Professor"=>1, "Professor > Associate Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>4, "Neuroscience"=>5, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>5}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1943014"], "description"=>"<p>(A-C) RT-PCR analysis of transcripts for Brpf1 (A), the acetyltransfrases Hbo1 and hMof (B), and five transcription factors (C), loss of which is known to cause dentate gyrus hypoplasia (see the text). The primers used are listed in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005034#pgen.1005034.s007\" target=\"_blank\">S1 Table</a>. Gapdh was used as the internal control [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005034#pgen.1005034.ref057\" target=\"_blank\">57</a>]. At P24, Tbr2 expression is known to be limited to the subgranular zone of the dentate gyrus, so the RT-PCR product was not detected. (D) RT-qPCR analysis of transcripts for Brpf1, four cell cycle inhibitors and six genes important for hippocampus development. The p16/19, p15 and six other genes were identified in the microarray analysis of dorsal brain cortices isolated from three pairs of wild-type and mutant pups at P4 [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005034#pgen.1005034.ref057\" target=\"_blank\">57</a>]. The RT-qPCR analysis was performed on three pairs of dorsal brain cortices at P12 and the average values are shown with standard deviation. Dct, dopachrome tautomerase; Cplx3, presynaptic protein complexin 3. *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001; ns, not statistically significant.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331072, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g009", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Brpf1_loss_deregulates_gene_expression_important_for_hippocampus_development_/1331072", "title"=>"Brpf1 loss deregulates gene expression important for hippocampus development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943012"], "description"=>"<p>(A-B) After injection with BrdU at E12.5, E14.5 and E16.5, pregnant mice were sacrificed at P0 for immunohistochemical analysis with an anti-BrdU monoclonal antibody. Representative images of the hippocampal regions are shown in (A) and the quantification results of three BrdU<sup>+</sup> progenitor populations, outlined as the primary matrix (1ry), secondary matrix (2ry) and tertiary matrix (3ry), are presented in (B). The tertiary matrix corresponds to the developing dentate gyrus. For each time point, the quantification was based on 2 pairs of control and mutant brains, with 4 or 5 matched sections per brain. (C-D) After injection with BrdU at P12, wild-type and mutant pups were sacrificed 1 h later for immunohistochemical analysis with the anti-BrdU antibody. Representative images of the hippocampal regions are shown in (C) and the quantification result of BrdU<sup>+</sup> S-phase cells at the subgranular zone (marked with the yellow dashed lines) is presented in (D). The quantification was based on 2 pairs of control and mutant pups, with 4 matched sections per pup. Scale bars, 200 μm; ns, not statistically significant; **<i>p</i><0.01; ***<i>p</i><0.001.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331070, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g007", "stats"=>{"downloads"=>3, "page_views"=>81, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_neuronal_migration_in_the_hippocampus_by_BrdU_labeling_/1331070", "title"=>"Analysis of neuronal migration in the hippocampus by BrdU labeling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943009"], "description"=>"<p>(A-C) Immunofluorescence microscopy to detect Sox2<sup>+</sup> neural stem cells (NSCs) on peri- or postnatal brain sections. At P0, Sox2<sup>+</sup> NSCs were enriched in the wild-type dentate gyrus (DG) and this population was smaller in the mutant, as quantified in (D). At P10 and P14, Sox2<sup>+</sup> NSCs settled in the control subgranular zone (SGZ), while in the mutant, the granule cell layers were hypoplastic and the SGZ harbored few Sox2<sup>+</sup> NSCs. (D) Quantification of Sox2<sup>+</sup> cells in the control and mutant dentate gyri at P0. There were significantly fewer Sox2<sup>+</sup> NSCs within the mutant dentate gyrus per section (right). The number of Sox2<sup>+</sup> cells per mm<sup>2</sup> within the dentate gyrus also significantly decreased (left). The quantification was based on three pairs of neonates and at least three matched sections per brain. **<i>p</i><0.01; ***<i>p</i><0.001. (E) In the hippocampus, Ctip2 expression was restricted to the CA regions and the suprapyramidal blade of the developing dentate gyrus (DG-s) at P0. (F) Quantification of Ctip2<sup>+</sup> cells in the wild-type and mutant suprapyramidal blades, outlined in (E), was based on three pairs of neonates and at least three matched sections per brain. ***<i>p</i><0.001. (G-I) Dcx expression in control and bKO brain sections at three developmental stages. In the mutant dentate gyrus, there were fewer Dcx<sup>+</sup> neuronal precursors apparently at P10 (H) and P24 (I). Scale bars: (A-C), 100 μm; (E), 400 μm, (G-I), 100 μm.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331067, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g004", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Brpf1_loss_compromises_neural_stem_cells_and_neuronal_precursors_/1331067", "title"=>"Brpf1 loss compromises neural stem cells and neuronal precursors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943008"], "description"=>"<p>(A-B) Nissl staining of coronal brain sections from E17.5 and P0 mice. At P0, loss of <i>Brpf1</i> resulted in underdevelopment of the suprapyramidal blade (sb) and disappearance of the infrapyramidal blade (ib) in the developing dentate gyrus. (C) Golgi-Cox staining of coronal brain sections at P19. Representative images of hippocampal regions from the wild-type and bKO brain sections show that the bKO hippocampus possessed disorganized neurons, with less robust dendritic trees. There were also fewer neurons in the mutant dentate gyrus. Red asterisks denote areas accidentally torn during staining. The boxed regions in the top panels are shown in the lower panels at higher magnification. (D-E) Ki67 immunohistochemistry showing that cell proliferation dramatically decreased in the subgranular zone of the bKO dentate gyrus at P10 and P24. The subgranular zones of the control P10 and P24 sections shown here contain 20 and 34 Ki67<sup>+</sup> cells, respectively, whereas the corresponding regions of the mutant sections possess either one or no Ki67<sup>+</sup> cells. Scale bars, 100 μm for (A-B & D-E) and 200 μm for (C).</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331066, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g003", "stats"=>{"downloads"=>0, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Brpf1_loss_impairs_dentate_gyrus_development_dendritic_tree_formation_and_neuronal_proliferation_/1331066", "title"=>"Brpf1 loss impairs dentate gyrus development, dendritic tree formation and neuronal proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943011"], "description"=>"<p>(A-D) Immunostaining to detect Tbr2<sup>+</sup> intermediate neuronal progenitors on sections from E13.5, E16.5, P0 and P10 brains. At E13.5 (A), Tbr2 was similarly expressed in the control and mutant neuroepithelium and hippocampus primordium (HP). At E16.5 (B), Tbr2 was similarly expressed in the control and mutant subventricular zones (SVZ) and hippocampi. At P0 and P10, there were fewer Tbr2<sup>+</sup> progenitors in the mutant dentate gyrus (C-D). The yellow arrowheads in the right two panels mark four progenitors that failed to settle in the subgranular zone, but stayed at the outer rim of the molecular cell layer. (E) Quantification of Tbr2<sup>+</sup> progenitors in the developing dentate gyrus at P0, outlined with clear dash lines in (C). While there was no significant difference in the cell density (right), the Tbr2<sup>+</sup> progenitor number per section decreased significantly in the mutant (left). The quantification was based on three pairs of control and mutant brains, with at least three matched sections per brain. **<i>p</i><0.01; ns, not statistically significant. (F-H) Immunofluorescence microscopy to detect NeuroD1<sup>+</sup> neuroblasts on E16.5, P10 and P24 brain sections. At E16.5 (F), NeuroD1 expression was relatively normal in the mutant hippocampus (HP), but it virtually disappeared in the mutant dentate gyrus at P10 (G) and P24 (H). DG, dentate gyrus; dNE, dentate neuroepithelium; dms, dentate migration stream; HP, hippocampus; sb, suprapyramidal blade; ib, infrapyramidal blade; SVZ, subventricular zone; scale bars, 100 μm.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331069, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g006", "stats"=>{"downloads"=>0, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Defective_Tbr2_and_NeuroD1_neuronal_precursors_in_the_mutant_hippocampus_/1331069", "title"=>"Defective Tbr2<sup>+</sup> and NeuroD1<sup>+</sup> neuronal precursors in the mutant hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943010"], "description"=>"<p>(A-C) Immunofluorescence microscopy to detect Gfap expression on brain sections at E16.5, P0 and P10. Distribution of Gfap<sup>+</sup> radial glial cells in the mutant dentate gyri was only slightly disturbed at E16.5 and moderately at P0 (A-B), but it became completely disorganized at P10 (C). (D) High-magnification images of the regions boxed in (C). Compared to the wild-type dentate gyrus, there were few Gfap<sup>+</sup> radial glial cells in the mutant (see the areas marked by asterisks). In addition, the hippocampus fissure (hf) was ill-formed in the mutant. HP, hippocampus; sb, suprapyramidal blade; scale bars, 100 μm.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331068, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g005", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Deregulated_Gfap_expression_in_the_mutant_hippocampus_/1331068", "title"=>"Deregulated Gfap expression in the mutant hippocampus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943007"], "description"=>"<p>(A-B) Nissl staining was performed on coronal brain sections from P10 and P24 mice. Loss of <i>Brpf1</i> resulted in underdevelopment of the suprapyramidal blade (sb) and disappearance of the infrapyramidal blade (ib) in the dentate gyrus. The border between cornu ammonis 1 (CA1) and the subiculum (SB) was clearly defined in the wild-type sections but became obscure in the mutant, as indicated by red arrowheads in (A). At P10 and P24, the pyramidal layers of CA1 and CA3 in the mutant sections were not as tightly packed as in the wild-type (A-B). (C-D) Nissl staining of serial brain sections. Five medial-to-lateral sagittal sections were prepared from P10 (C) or P24 (D) wild-type and mutant brains and Nissl-stained to analyze the morphology of the hippocampus at different planes (A). The border between CA1 and the subiculum, marked by red arrowheads, was clearly defined in the wild-type but not mutant sections. v, ventral hippocampus; d, dorsal hippocampus. Scale bars, 100 μm for (A-B) and 0.5 mm for (C-D).</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331065, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g002", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forebrain_specific_Brpf1_loss_causes_hypoplasia_of_the_dentate_gyrus_/1331065", "title"=>"Forebrain-specific Brpf1 loss causes hypoplasia of the dentate gyrus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943006"], "description"=>"<p>(A) At E14.5, β-galactosidase activity (labeled blue, with nuclei stained red) was detected in the marginal zone (MZ) of the cortical hem, but not in the developing neocortex. In the hippocampus, the signal was detected sparsely in the dentate migration stream (dms, marked by a curved arrow). (B) At E17.5, the expression is very weak in the neocortex and hippocampus. Note the sparse signals detected in the dentate migration stream (dms) marked by a curved arrow. (C-E) After birth, β-galactosidase activity appeared in the neocortex and hippocampus. From P3 onwards, β-galactosidase activity was detected in all the six layers of neocortex and in the cornum amonni (CA) field of the hippocampus. The activity in the dentate gyrus was moderate at P3 but became much stronger at P14 and adult. All images were taken from frozen sections prepared from <i>Brpf1</i><sup><i>l/+</i></sup> embryos (A-B) or postnatal brains (C-E); the corresponding wild-type sections showed no β-galactosidase staining [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005034#pgen.1005034.ref055\" target=\"_blank\">55</a>]. Structures of the developing and adult brains were annotated according to published atlases [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005034#pgen.1005034.ref087\" target=\"_blank\">87</a>–<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005034#pgen.1005034.ref091\" target=\"_blank\">91</a>]. CA1, cornum amonni 1; CA3, cornum amonni 3; CP, cortical plate; DG, dentate gyrus; DG-g, granular cell layer of dentate gyrus; DG-m, molecular layer of dentate gyrus; HP, hippocampus; I-IV, cortical layers I-VI; IZ, intermediate zone; Rad, radial layer of the hippocampus; SVZ, subventricular zone; VZ, ventricular zone. Scale bars, 100 μm.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331064, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g001", "stats"=>{"downloads"=>0, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Brpf1_expression_during_forebrain_development_/1331064", "title"=>"<i>Brpf1</i> expression during forebrain development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943015", "https://ndownloader.figshare.com/files/1943016", "https://ndownloader.figshare.com/files/1943017", "https://ndownloader.figshare.com/files/1943018", "https://ndownloader.figshare.com/files/1943019", "https://ndownloader.figshare.com/files/1943020", "https://ndownloader.figshare.com/files/1943021", "https://ndownloader.figshare.com/files/1943022"], "description"=>"<div><p>Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the <i>MOZ</i> and <i>MORF</i> genes are rearranged in leukemia, the <i>MORF</i> gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse <i>Brpf1</i> gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2<sup>+</sup> neural stem cells and Tbr2<sup>+</sup> intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.</p></div>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331073, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005034.s001", "https://dx.doi.org/10.1371/journal.pgen.1005034.s002", "https://dx.doi.org/10.1371/journal.pgen.1005034.s003", "https://dx.doi.org/10.1371/journal.pgen.1005034.s004", "https://dx.doi.org/10.1371/journal.pgen.1005034.s005", "https://dx.doi.org/10.1371/journal.pgen.1005034.s006", "https://dx.doi.org/10.1371/journal.pgen.1005034.s007", "https://dx.doi.org/10.1371/journal.pgen.1005034.s008"], "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Lysine_Acetyltransferase_Activator_Brpf1_Governs_Dentate_Gyrus_Development_through_Neural_Stem_Cells_and_Progenitors_/1331073", "title"=>"The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-03-10 03:40:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1943013"], "description"=>"<p>(A-B) After BrdU labeling, E15.5 pregnant mice were sacrificed 1 h later to retrieve fetal brains for subsequent fixing and sectioning. Immunofluorescence microscopy was performed with anti-Ki67 and-BrdU antibodies, with representative images of the hippocampal regions shown in (A) and the quantification of the stained cells in two regions (outlined with dotted lines) presented in (B). The quantification was based on two pairs of control and mutant brains, with 8 matched sections per brain. In the dentate neuroepithelium (dNE), no difference was detected. In the dentate migration stream (dms), the number of BrdU<sup>+</sup> progenitors was normal but the Ki67<sup>+</sup> cycling cells increased significantly, thereby decreasing the ratio of S-phase (BrdU<sup>+</sup>) vs proliferating (Ki67<sup>+</sup>) cells. (C-D) Immunostaining of sections from the same brains as in (A-B) with an antibody specific to phospho-Ser10 of histone H3 (pH3). Representative images of the hippocampal regions are shown in (C) and the quantification of positive cells in two regions (outlined with dashed lines) is presented in (D). No pH3-positive cells were detected in the migration stream. Scale bars: 100 μm; ns, not statistically significant; *<i>p</i><0.05, **<i>p</i><0.01.</p>", "links"=>[], "tags"=>["hbo", "results link histone binding", "Neural stem cells", "mouse Brpf 1 gene causes hypoplasia", "phd", "hippocampu", "multidomain histone binder", "moz", "morf", "BRPF", "Lysine Acetyltransferase Activator Brpf 1 Governs Dentate Gyrus Development", "dentate gyrus", "Brpf 1 loss deregulates", "Progenitors Lysine acetylation", "KAT 6A KAT 6B", "cell cycle progression"], "article_id"=>1331071, "categories"=>["Biological Sciences"], "users"=>["Linya You", "Kezhi Yan", "Jinfeng Zhou", "Hong Zhao", "Nicholas R. Bertos", "Morag Park", "Edwin Wang", "Xiang-Jiao Yang"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005034.g008", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_cycle_properties_and_progenitor_number_in_the_mutant_dentate_gyrus_/1331071", "title"=>"Cell cycle properties and progenitor number in the mutant dentate gyrus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-10 03:40:28"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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