OLIG2 regulates lncRNAs and its own expression during oligodendrocyte lineage formation

BMC Biology

Natasha Kharas¹  Xizi Wu²  Bo Hai²  Xiaomin Dong²  Haichao Wei²  Yanan You²  Jia Qian Wu³  Raquel Cuevas-Diaz Duran⁴ 

[1] Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, TX, USA;MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA;The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA;Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX, USA;The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA;Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX, USA;MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA;The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA;Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX, USA;Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L., Mexico;

关键词: Oligodendrocyte development;    OLIG2;    LncRNAs;    Histone modification;    Transcriptional regulation;    Regulation after transcription;   

DOI  :  10.1186/s12915-021-01057-6

来源: Springer

【 摘 要 】

BackgroundOligodendrocytes, responsible for axon ensheathment, are critical for central nervous system (CNS) development, function, and diseases. OLIG2 is an important transcription factor (TF) that acts during oligodendrocyte development and performs distinct functions at different stages. Previous studies have shown that lncRNAs (long non-coding RNAs; > 200 bp) have important functions during oligodendrocyte development, but their roles have not been systematically characterized and their regulation is not yet clear.ResultsWe performed an integrated study of genome-wide OLIG2 binding and the epigenetic modification status of both coding and non-coding genes during three stages of oligodendrocyte differentiation in vivo: neural stem cells (NSCs), oligodendrocyte progenitor cells (OPCs), and newly formed oligodendrocytes (NFOs). We found that 613 lncRNAs have OLIG2 binding sites and are expressed in at least one cell type, which can potentially be activated or repressed by OLIG2. Forty-eight of them have increased expression in oligodendrocyte lineage cells. Predicting lncRNA functions by using a “guilt-by-association” approach revealed that the functions of these 48 lncRNAs were enriched in “oligodendrocyte development and differentiation.” Additionally, bivalent genes are known to play essential roles during embryonic stem cell differentiation. We identified bivalent genes in NSCs, OPCs, and NFOs and found that some bivalent genes bound by OLIG2 are dynamically regulated during oligodendrocyte development. Importantly, we unveiled a previously unknown mechanism that, in addition to transcriptional regulation via DNA binding, OLIG2 could self-regulate through the 3′ UTR of its own mRNA.ConclusionsOur studies have revealed the missing links in the mechanisms regulating oligodendrocyte development at the transcriptional level and after transcription. The results of our research have improved the understanding of fundamental cell fate decisions during oligodendrocyte lineage formation, which can enable insights into demyelination diseases and regenerative medicine.

【 授权许可】

CC BY