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Dynamic Lamin B1-Gene Association During Oligodendrocyte Progenitor Differentiation

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Abstract

Differentiation of oligodendrocytes (OL) from progenitor cells (OPC) is the result of a unique program of gene expression, which is further regulated by the formation of topological domains of association with the nuclear lamina. In this study, we show that cultured OPC were characterized by progressively declining levels of endogenous Lamin B1 (LMNB1) during differentiation into OL. We then identify the genes dynamically associated to the nuclear lamina component LMNB1 during this transition, using a well established technique called DamID, which is based on the ability of a bacterially-derived deoxyadenosine methylase (Dam), to modify genomic regions in close proximity. We expressed a fusion protein containing Dam and LMNB1 in OPC (OPCLMNB1-Dam) and either kept them proliferating or differentiated them into OL (OLLMNB1-Dam) and identified genes that were dynamically associated to LMNB1 with differentiation. Importantly, we identified Lss, the gene encoding for lanosterol synthase, a key enzyme in cholesterol synthesis, as associated to the nuclear lamina in OLLMNB1-Dam. This finding could at least in part explain the lipid dysregulation previously reported for mouse models of ADLD characterized by persistent LMNB1 expression in oligodendrocytes.

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Acknowledgments

The authors would like to thank Drs. Bas van Steensel and Daan Peric-Hupkes for generous sharing of reagents and protocols and for providing invaluable suggestions. This work was supported by Grant R35 NS111604 to PC.

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Authors and Affiliations

  1. Neuroscience Initiative at the Advanced Science Research Center of the Graduate Center of the City University of New York, 85 St. Nicholas Terrace, New York, NY, 10031, USA

    Camila Yattah, Dennis Huang, HyeJin Park & Patrizia Casaccia

  2. Graduate Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY, 10016, USA

    Camila Yattah & Dennis Huang

  3. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Marylens Hernandez & Patrizia Casaccia

  4. New York Genome Center, New York, NY, 10013, USA

    Will Liao

  5. Graduate Program in Biochemistry and in Biology, The Graduate Center of The City University of New York, 365 5th Avenue, New York, NY, 10016, USA

    Patrizia Casaccia

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Yattah, C., Hernandez, M., Huang, D. et al. Dynamic Lamin B1-Gene Association During Oligodendrocyte Progenitor Differentiation. Neurochem Res 45, 606–619 (2020). https://doi.org/10.1007/s11064-019-02941-y

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