GROUP DESCRIPTION

The work in our lab focuses on understanding how the epigenome regulates embryonic development, cell differentiation, and disease, with a particular emphasis on DNA methylation as a stable and heritable regulator of gene activity. We are particularly interested in how DNA methylation patterns are established, maintained, and dynamically reprogrammed during key developmental transitions, including early embryogenesis and tissue differentiation. A central area of our research is atypical DNA methylation (mCH), and its role in regulating embryonic genome function. We investigate how these non-canonical marks are written and interpreted in vivo, and how they contribute to processes such as zygotic genome activation and neural development. In parallel, we are interested in the evolutionary aspects of epigenetic regulation, particularly how different vertebrate species reset and re-establish their epigenomes during early development.

GROUP OBJECTIVES

By integrating functional genomics, genetic models, and comparative (evo-devo) approaches, we aim to uncover fundamental and evolutionarily conserved principles of epigenetic control during embryonic development.

RESEARCH GROUP MEMBERS

Lab head

Ozren Bogdanovic

Predoctoral researcher

Estela Moreno Aparicio

Predoctoral researcher

Thirsa Brethouwer

Postdoctoral Researcher

Maria Exposito Serrano

Bioinformatician

Jesús García Junco

Bioinformatician

Cristina Lupiáñez

DANIO-ReCODE Project Manager

Encarni Carillo Nieto

Lab Manager

Marta Carmona Padilla

RESEARCH LINES

  1. Atypical DNA methylation as a regulator of embryonic genome functionWe have recently described embryonic reprogramming of non-canonical DNA methylation (mCH, where H = C, T, A) within mosaic satellite repeats (MOSAT), coincident with zygotic genome activation. We are now functionally interrogating the contribution of mCH to embryogenesis, to better understand the developmental requirements for proper mCH patterning.
  2. Dissecting the function of atypical DNA methylation “reading” and “writing” in vivo.
    We have previously shown that in zebrafish brains, non-CpG methylation (mCH), specifically mCAC, is enriched at distinct transposon motifs and in developmentally downregulated genes associated with neural and developmental functions. Building on these findings, we are now generating zebrafish mutants deficient in mCH readers such as mecp2, as well as stable double Dnmt3aa/ab knockouts, which in zebrafish exhibit redundancy in maintaining mCG patterns. These unique genetic contexts enable us to selectively perturb mCH writing and reading without globally disrupting canonical DNA methylation.
  3. Evolution of embryonic epigenome reprogramming
    We are exploring how epigenomes are established during the earliest stages of embryogenesis across a range of vertebrate species, with the goal of uncovering both conserved principles and lineage-specific innovations. By comparing these strategies, we aim to gain fundamental insights into the molecular logic of developmental plasticity.

PROJECTS

2026 – 2028       A/Prof Andrew Cox (Chief Investigator), Monash University, A/Prof Jan Kaslin (Chief Investigator) Monash University, A/Prof Ozren Bogdanovic (Partner Investigator): Metabolic control of cell plasticity in embryogenesis and tissue repair. Australian Research Council Discovery Project DP260102257.

2026 – 2027       Ozren Bogdanovic (PI): A toolbox for understanding the in vivo function of non-canonical DNA methylation. Proyecto Europa Excelencia. Spanish Ministry of Science, Innovation and Universities EUR2025-165036.

2026 – 2028       Ozren Bogdanovic (PI): The form and function of non-canonical DNA methylation during neural development. Proyectos de Generación de Conocimiento, Spanish Ministry of Science, Innovation and Universities PID2024-162911NB-I00.

2025 – 2027       Dr Ksenia Skvortsova (Chief Investigator – CI), A/Prof Tim Hore (Partner Investigator – PI), A/Prof Ozren Bogdanovic (Partner Investigator): Evolution of the epigenetic regulation in the female immune system. Australian Research Council Discovery Project DP250102459; (€255,000).

2024 – 2026       Ozren Bogdanovic (PI): Plataforma de generación y fenotipado de modelos animales mediante genómica funcional de alto rendimiento. Proyecto Adquisición de equipamiento científico-tecnológico. Spanish Ministry of Science, Innovation and Universities EQC2024-008579-P.

2024 – 2028       Ozren Bogdanovic (PI and Network Coordinator): DANIO-ReCODE: The next frontier: Decoding transcription regulation in regeneration by advanced genomics tools. MSCA Doctoral Network 2023, Horizon Europe 101169349.

2024 – 2026       Ozren Bogdanovic (PI): Structure, function, and evolution of invertebrate CpG islands – invert-CGI. Proyecto Consolidation Investigadora, Spanish Ministry of Science, Innovation and Universities CNS202300X144039IV0.

PUBLICATIONS

1: Burgos-Ruiz AM, Geng FS, Pujol G, Sanabria E, Brethouwer T, Almuedo-Castillo M, Ruiz-Herrera A, Tena JJ, Bogdanovic O. A single-cell multiomics roadmap of zebrafish spermatogenesis reveals regulatory principles of male germline formation. Mol Syst Biol. 2026 Jan;22(1):42-68. doi: 10.1038/s44320-025-00157-7. Epub 2025 Oct 14. PMID: 41087739; PMCID: PMC12759076.

2: Brethouwer T, de Mendoza A, Bogdanovic O. Non-CG DNA methylation in animal genomes. Nat Genet. 2025 Oct;57(10):2395-2407. doi: 10.1038/s41588-025-02303-1. Epub 2025 Sep 11. PMID: 40935851.

3: Angeloni A, Fissette S, Kaya D, Hammond JM, Gamaarachchi H, Deveson IW, Klose RJ, Li W, Zhang X, Bogdanovic O. Extensive DNA methylome rearrangement during early lamprey embryogenesis. Nat Commun. 2024 Mar 4;15(1):1977. doi:10.1038/s41467-024-46085-2. PMID: 38438347; PMCID: PMC10912607.

4: Ross SE, Vázquez-Marín J, Gert KRB, González-Rajal Á, Dinger ME, Pauli A, Martínez-Morales JR, Bogdanovic O. Evolutionary conservation of embryonic DNA methylome remodelling in distantly related teleost species. Nucleic Acids Res. 2023 Oct 13;51(18):9658-9671. doi: 10.1093/nar/gkad695. PMID: 37615576; PMCID: PMC10570028.

5: Skvortsova K, Bertrand S, Voronov D, Duckett PE, Ross SE, Magri MS, Maeso I, Weatheritt RJ, Gómez Skarmeta JL, Arnone MI, Escriva H, Bogdanovic O. Active DNA demethylation of developmental cis-regulatory regions predates vertebrate origins. Sci Adv. 2022 Dec 2;8(48):eabn2258. doi: 10.1126/sciadv.abn2258. Epub 2022 Dec 2. PMID: 36459547; PMCID: PMC10936051.

6: Ross SE, Angeloni A, Geng FS, de Mendoza A, Bogdanovic O. Developmental remodelling of non-CG methylation at satellite DNA repeats. Nucleic Acids Res. 2020 Dec 16;48(22):12675-12688. doi: 10.1093/nar/gkaa1135. PMID: 33271598; PMCID: PMC7736785.

7: de Mendoza A, Lister R, Bogdanovic O. Evolution of DNA Methylome Diversity in Eukaryotes. J Mol Biol. 2020 Mar 13;432(6):1687-1705. doi: 10.1016/j.jmb.2019.11.003. Epub 2019 Nov 11. PMID: 31726061.

8: Skvortsova K, Tarbashevich K, Stehling M, Lister R, Irimia M, Raz E, Bogdanovic O. Retention of paternal DNA methylome in the developing zebrafish germline. Nat Commun. 2019 Jul 11;10(1):3054. doi: 10.1038/s41467-019-10895-6. PMID: 31296860; PMCID: PMC6624265.

9: Skvortsova K, Iovino N, Bogdanović O. Functions and mechanisms of epigenetic inheritance in animals. Nat Rev Mol Cell Biol. 2018 Dec;19(12):774-790. doi:10.1038/s41580-018-0074-2. PMID: 30425324.

10: Ross SE, Hesselson D, Bogdanovic O. Developmental Accumulation of Gene Body and Transposon Non-CpG Methylation in the Zebrafish Brain. Front Cell Dev Biol. 2021 Mar 4;9:643603. doi: 10.3389/fcell.2021.643603. PMID: 33748137; PMCID:PMC7978034.