title: Epigenetic regulation by chromatin activation mark H3K4me3 in primate progenitor cells within adult neurogenic niche.
abstract: Histone 3 lysine 4 trimethylation (H3K4me3) is known to be associated with transcriptionally active or poised genes and required for postnatal neurogenesis within the subventricular zone (SVZ) in the rodent model. Previous comparisons have shown significant correlation between baboon (Papio anubis) and human brain. In this study, we demonstrate that chromatin activation mark H3K4me3 is present in undifferentiated progenitor cells within the SVZ of adult baboon brain. To identify the targets and regulatory role of H3K4me3 within the baboon SVZ, we developed a technique to purify undifferentiated SVZ cells while preserving the endogenous nature without introducing culture artifact to maintain the in vivo chromatin state for genome-wide studies (ChIP-Seq and RNA-Seq). Overall, H3K4me3 is significantly enriched for genes involved in cell cycle, metabolism, protein synthesis, signaling pathways, and cancer mechanisms. Additionally, we found elevated levels of H3K4me3 in the MRI-classified SVZ-associated Glioblastoma Multiforme (GBM), which has a transcriptional profile that reflects the H3K4me3 modifications in the undifferentiated progenitor cells of the baboon SVZ. Our findings highlight the importance of H3K4me3 in coordinating distinct networks and pathways for life-long neurogenesis, and suggest that subtypes of GBM could occur, at least in part, due to aberrant H3K4me3 epigenetic regulation.
authors.affiliation: Department of Genome Sciences, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Sandstrom
authors.affiliation: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Foret
authors.affiliation: 1] Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA [2] Neuroscience Institute, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Grow
authors.affiliation: Department of Genome Sciences, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Haugen
authors.affiliation: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Rhodes
authors.affiliation: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA.
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Cardona
authors.affiliation: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA.
authors.forename: Clyde F
authors.initials: CF
authors.lastname: Phelix
authors.affiliation: Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.affiliation: 1] Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA [2] Neuroscience Institute, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
authors.forename: Chin-Hsing Annie
authors.initials: CH
authors.lastname: Lin
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006657:Histones / Q000235:genetics*; D020547:Lateral Ventricles / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics*; D048530:Papio anubis; D055153:Stem Cell Niche / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D002843:Chromatin; D005819:Genetic Markers; D006657:Histones