title: Synaptonemal complex assembly and H3K4Me3 demethylation determine DIDO3 localization in meiosis.
abstract: Synapsis of homologous chromosomes is a key meiotic event, mediated by a large proteinaceous structure termed the synaptonemal complex. Here, we describe a role in meiosis for the murine death-inducer obliterator (Dido) gene. The Dido gene codes for three proteins that recognize trimethylated histone H3 lysine 4 through their amino-terminal plant homeodomain domain. DIDO3, the largest of the three isoforms, localizes to the central region of the synaptonemal complex in germ cells. DIDO3 follows the distribution of the central region protein SYCP1 in Sycp3-/- spermatocytes, which lack the axial elements of the synaptonemal complex. This indicates that synapsis is a requirement for DIDO3 incorporation. Interestingly, DIDO3 is missing from the synaptonemal complex in Atm mutant spermatocytes, which form synapses but show persistent trimethylation of histone H3 lysine 4. In order to further address a role of epigenetic modifications in DIDO3 localization, we made a mutant of the Dido gene that produces a truncated DIDO3 protein. This truncated protein, which lacks the histone-binding domain, is incorporated in the synaptonemal complex irrespective of histone trimethylation status. DIDO3 protein truncation in Dido mutant mice causes mild meiotic defects, visible as gaps in the synaptonemal complex, but allows for normal meiotic progression. Our results indicate that histone H3 lysine 4 demethylation modulates DIDO3 localization in meiosis and suggest epigenetic regulation of the synaptonemal complex.
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, 28049 Madrid, Spain.
authors: Ignacio
authors: I
authors: Prieto
authors: Anna
authors: A
authors: Kouznetsova
authors: Agnes
authors: A
authors: Fütterer
authors: Varvara
authors: V
authors: Trachana
authors: Esther
authors: E
authors: Leonardo
authors: Astrid
authors: A
authors: Alonso Guerrero
authors: Mercedes
authors: M
authors: Cano Gamero
authors: Cristina
authors: C
authors: Pacios-Bras
authors: Hervé
authors: H
authors: Leh
authors: Malcolm
authors: M
authors: Buckle
authors: Mónica
authors: M
authors: Garcia-Gallo
authors: Leonor
authors: L
authors: Kremer
authors: Antonio
authors: A
authors: Serrano
authors: Fernando
authors: F
authors: Roncal
authors: Juan Pablo
authors: JP
authors: Albar
authors: José Luis
authors: JL
authors: Barbero
authors: Carlos
authors: C
authors: Martínez-A
authors: Karel H M
authors: KH
authors: van Wely
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics*; D008239:Lysine / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology*; D008745:Methylation; D051379:Mice; D013090:Spermatocytes / Q000378:metabolism; D013573:Synaptonemal Complex / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C120687:Dido protein, mouse; D006657:Histones; D014157:Transcription Factors; D008239:Lysine