4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The proper regulation of spermatogenesis is crucial to ensure the continued production of sperm and fertility. Here, we investigated the function of the H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to fewer spermatogonia and germ cell loss before 3 weeks of age. These results demonstrate that KDM1A is required for spermatogonial differentiation, as well as germ cell survival, in the developing testis. In addition, inducible deletion of Kdm1a in the adult testis results in the abnormal accumulation of meiotic spermatocytes, as well as apoptosis and progressive germ cell loss. These results demonstrate that KDM1A is also required during adult spermatogenesis. Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained in differentiating germ cells. This requirement for KDM1A is similar to what has been observed in other stem cell populations, suggesting a common function. Taken together, we propose that KDM1A is a key regulator of spermatogenesis and germ cell maintenance in the mouse.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          The diverse functions of histone lysine methylation.

          Covalent modifications of histone tails have fundamental roles in chromatin structure and function. One such modification, lysine methylation, has important functions in many biological processes that include heterochromatin formation, X-chromosome inactivation and transcriptional regulation. Here, we summarize recent advances in our understanding of how lysine methylation functions in these diverse biological processes, and raise questions that need to be addressed in the future.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Histone demethylation mediated by the nuclear amine oxidase homolog LSD1.

            Posttranslational modifications of histone N-terminal tails impact chromatin structure and gene transcription. While the extent of histone acetylation is determined by both acetyltransferases and deacetylases, it has been unclear whether histone methylation is also regulated by enzymes with opposing activities. Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant derepression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline.

              Small RNAs associate with Argonaute proteins and serve as sequence-specific guides for regulation of mRNA stability, productive translation, chromatin organization, and genome structure. In animals, the Argonaute superfamily segregates into two clades. The Argonaute clade acts in RNAi and in microRNA-mediated gene regulation in partnership with 21-22 nt RNAs. The Piwi clade, and their 26-30 nt piRNA partners, have yet to be assigned definitive functions. In mice, two Piwi-family members have been demonstrated to have essential roles in spermatogenesis. Here, we examine the effects of disrupting the gene encoding the third family member, MIWI2. Miwi2-deficient mice display a meiotic-progression defect in early prophase of meiosis I and a marked and progressive loss of germ cells with age. These phenotypes may be linked to an inappropriate activation of transposable elements detected in Miwi2 mutants. Our observations suggest a conserved function for Piwi-clade proteins in the control of transposons in the germline.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 May 2017
                2017
                : 12
                : 5
                : e0177473
                Affiliations
                [1 ]Cell Biology Department, Emory University, Atlanta, Georgia, United States of America
                [2 ]Graduate Division of Biological and Biomedical Science, Emory University, Atlanta, Georgia, United States of America
                [3 ]Biology Department, Emory University, Atlanta, Georgia, United States of America
                University Hospital of Münster, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: DAM DJK.

                • Data curation: DAM DJK.

                • Formal analysis: DAM DJK.

                • Funding acquisition: WGK DJK.

                • Investigation: DAM MAC AKS PGD DJK AMS.

                • Methodology: DAM DJK.

                • Project administration: DAM DJK.

                • Resources: DJK WGK.

                • Supervision: DJK.

                • Validation: DAM DJK.

                • Visualization: DAM DJK.

                • Writing – original draft: DAM DJK.

                • Writing – review & editing: DAM DJK.

                Author information
                http://orcid.org/0000-0002-3040-1142
                Article
                PONE-D-16-47104
                10.1371/journal.pone.0177473
                5428937
                28498828
                b8918d83-ff56-442d-b0d7-0d522f0125b2
                © 2017 Myrick et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 November 2016
                : 27 April 2017
                Page count
                Figures: 6, Tables: 0, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: IOS1354998
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5R25GM089615-04
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: T32GM008490-21
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5T32GM008367
                Award Recipient :
                D. Myrick was a member of the PREP post-baccalaureate program (5R25GM089615-04). M. Christopher is supported by the GMB training grant (T32GM008490-21). P. Donlin-Asp was supported by the BCDB training grant (5T32GM008367). The work was supported by a grant to D.J.K from the National Science Foundation (IOS1354998).
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Germ Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Germ Cells
                Sperm
                Spermatogonia
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Genital Anatomy
                Testes
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Genital Anatomy
                Testes
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Cycle and Cell Division
                Meiosis
                Spermatogenesis
                Biology and Life Sciences
                Cell Biology
                Chromosome Biology
                Meiosis
                Spermatogenesis
                Biology and Life Sciences
                Physiology
                Reproductive Physiology
                Spermatogenesis
                Medicine and Health Sciences
                Physiology
                Reproductive Physiology
                Spermatogenesis
                Biology and Life Sciences
                Developmental Biology
                Cell Differentiation
                Biology and life sciences
                Cell biology
                Chromosome biology
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                Epigenetics
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                Gene expression
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                DNA
                DNA modification
                DNA methylation
                Biology and life sciences
                Biochemistry
                Nucleic acids
                DNA
                DNA modification
                DNA methylation
                Biology and life sciences
                Genetics
                Epigenetics
                DNA modification
                DNA methylation
                Biology and life sciences
                Genetics
                Gene expression
                DNA modification
                DNA methylation
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Genital Anatomy
                Seminiferous Tubules
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Genital Anatomy
                Seminiferous Tubules
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Death
                Apoptosis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article