Synaptonemal complex assembly and H3K4Me3 demethylation determine DIDO3 localization in meiosis

• Published in: Chromosoma Vol. 118; no. 5; pp. 617 - 632
• Main Authors: Prieto, Ignacio, Kouznetsova, Anna, Fütterer, Agnes, Trachana, Varvara, Leonardo, Esther, Alonso Guerrero, Astrid, Cano Gamero, Mercedes, Pacios-Bras, Cristina, Leh, Hervé, Buckle, Malcolm, Garcia-Gallo, Mónica, Kremer, Leonor, Serrano, Antonio, Roncal, Fernando, Albar, Juan Pablo, Barbero, José Luis, Martínez-A, Carlos, van Wely, Karel H. M
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.10.2009; Springer-Verlag; Springer Nature B.V
• Subjects: Amino Acid Sequence; Animal Genetics and Genomics; Animals; Biochemistry; Biomedical and Life Sciences; Cell Biology; Developmental Biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epigenesis, Genetic; Eukaryotic Microbiology; Histones - genetics; Human Genetics; Life Sciences; Lysine - metabolism; Male; Medicin och hälsovetenskap; Meiosis - physiology; Methylation; Mice; Research Article; Spermatocytes - metabolism; Synaptonemal Complex - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Green Fluorescent Protein; Fluorescence Resonance Energy Transfer; Germ Cell Apoptosis; Pachytene Spermatocyte; Synaptonemal Complex
• ISSN: 0009-5915; 1432-0886; 1432-0886
• DOI: 10.1007/s00412-009-0223-7

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.