Identification of Genome-wide Targets of Olig2 in the Adult Mouse Spinal Cord Using ChIP-Seq

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Oct 20

PMID 29049317

Citations 7

Authors

Andrew J Darr

Matt C Danzi

Lee Brady

Dorothea Emig-Agius

Amber Hackett

Roozbeh Golshani

Nikita Warner

Jae Lee

Vance P Lemmon

Pantelis Tsoulfas

Affiliations

Soon will be listed here.

Abstract

In jawed vertebrates, oligodendrocytes (OLs) are the myelin-producing glial cells responsible for ensheathment of axons within the central nervous system and are also crucial for remyelination following injury or disease. Olig2 is a crucial factor in the specification and differentiation of oligodendrocyte precursor cells (OPCs) that give rise to mature, myelin-producing OLs in the developing and postnatal CNS; however, its role in adulthood is less well understood. To investigate the role Olig2 plays in regulating gene expression in the adult OL lineage in a physiologically-relevant context, we performed chromatin immunoprecipitation followed by next generation sequencing analysis (ChIP-Seq) using whole spinal cord tissue harvested from adult mice. We found that many of the Olig2-bound sites were associated with genes with biological processes corresponding to OL differentiation (Nkx2.2, Nkx6.2, and Sip1), myelination and ensheathment (Mbp, Cldn11, and Mobp), as well as cell cycle and cytoskeletal regulation. This suggests Olig2 continues to play a critical role in processes related to OL differentiation and myelination well into adulthood.

Citing Articles

Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179.

Li Y, Lim C, Dismuke T, Malawsky D, Oasa S, Bruce Z Nat Commun. 2025; 16(1):1091.

PMID: 39904981 PMC: 11794477. DOI: 10.1038/s41467-024-54861-3.

Evolutionary Origins of the Oligodendrocyte Cell Type and Adaptive Myelination.

Hines J Front Neurosci. 2021; 15:757360.

PMID: 34924932 PMC: 8672417. DOI: 10.3389/fnins.2021.757360.

STAU2 binds a complex RNA cargo that changes temporally with production of diverse intermediate progenitor cells during mouse corticogenesis.

Chowdhury R, Wang Y, Campbell M, Goderie S, Doyle F, Tenenbaum S Development. 2021; 148(15).

PMID: 34345913 PMC: 8353167. DOI: 10.1242/dev.199376.

Olig2 knockdown alleviates hypoxic-ischemic brain damage in newborn rats.

Yang L, Cui H Histol Histopathol. 2021; 36(6):675-684.

PMID: 34013967 DOI: 10.14670/HH-18-344.

Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues.

Bartosovic M, Kabbe M, Castelo-Branco G Nat Biotechnol. 2021; 39(7):825-835.

PMID: 33846645 PMC: 7611252. DOI: 10.1038/s41587-021-00869-9.

References

Fan H, Chen L, Qu X, Ren C, Wu X, Dong F . Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model. Sci Rep. 2017; 7:41407. PMC: 5286453. DOI: 10.1038/srep41407. View

Le Douarin N . Oligodendrocyte precursors originate from both the dorsal and the ventral parts of the spinal cord. Neuron. 1995; 15(6):1299-310. DOI: 10.1016/0896-6273(95)90009-8. View

Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X . Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell. 2013; 152(1-2):248-61. PMC: 3553550. DOI: 10.1016/j.cell.2012.12.006. View

Takebayashi H, Nabeshima Y, Yoshida S, Chisaka O, Ikenaka K, Nabeshima Y . The basic helix-loop-helix factor olig2 is essential for the development of motoneuron and oligodendrocyte lineages. Curr Biol. 2002; 12(13):1157-63. DOI: 10.1016/s0960-9822(02)00926-0. View

Masahira N, Takebayashi H, Ono K, Watanabe K, Ding L, Furusho M . Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells. Dev Biol. 2006; 293(2):358-69. DOI: 10.1016/j.ydbio.2006.02.029. View

Thakurela S, Garding A, Jung R, Muller C, Goebbels S, White R . The transcriptome of mouse central nervous system myelin. Sci Rep. 2016; 6:25828. PMC: 4865983. DOI: 10.1038/srep25828. View

Mazzoni E, Mahony S, Iacovino M, Morrison C, Mountoufaris G, Closser M . Embryonic stem cell-based mapping of developmental transcriptional programs. Nat Methods. 2011; 8(12):1056-8. PMC: 3228994. DOI: 10.1038/nmeth.1775. View

Cai J, Qi Y, Hu X, Tan M, Liu Z, Zhang J . Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron. 2005; 45(1):41-53. DOI: 10.1016/j.neuron.2004.12.028. View

Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden T . Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012; 13:134. PMC: 3412702. DOI: 10.1186/1471-2105-13-134. View

10.

Mehta S, Huillard E, Kesari S, Maire C, Golebiowski D, Harrington E . The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell. 2011; 19(3):359-71. PMC: 3070398. DOI: 10.1016/j.ccr.2011.01.035. View

11.

Cai J, Chen Y, Cai W, Hurlock E, Wu H, Kernie S . A crucial role for Olig2 in white matter astrocyte development. Development. 2007; 134(10):1887-99. DOI: 10.1242/dev.02847. View

12.

Ligon K, Huillard E, Mehta S, Kesari S, Liu H, Alberta J . Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron. 2007; 53(4):503-17. PMC: 1810344. DOI: 10.1016/j.neuron.2007.01.009. View

13.

Lau P, Verrier J, Nielsen J, Johnson K, Notterpek L, Hudson L . Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci. 2008; 28(45):11720-30. PMC: 2646797. DOI: 10.1523/JNEUROSCI.1932-08.2008. View

14.

Lecca D, Trincavelli M, Gelosa P, Sironi L, Ciana P, Fumagalli M . The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair. PLoS One. 2008; 3(10):e3579. PMC: 2570486. DOI: 10.1371/journal.pone.0003579. View

15.

Suva M, Rheinbay E, Gillespie S, Patel A, Wakimoto H, Rabkin S . Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell. 2014; 157(3):580-94. PMC: 4004670. DOI: 10.1016/j.cell.2014.02.030. View

16.

Xin M, Yue T, Ma Z, Wu F, Gow A, Lu Q . Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice. J Neurosci. 2005; 25(6):1354-65. PMC: 6725991. DOI: 10.1523/JNEUROSCI.3034-04.2005. View

17.

Bifulco M, Laezza C, Stingo S, Wolff J . 2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin. Proc Natl Acad Sci U S A. 2002; 99(4):1807-12. PMC: 122275. DOI: 10.1073/pnas.042678799. View

18.

Deng X, Wei H, Lou D, Sun B, Chen H, Zhang Y . Changes in CLIP3 expression after sciatic nerve injury in adult rats. J Mol Histol. 2012; 43(6):669-79. DOI: 10.1007/s10735-012-9450-y. View

19.

Waxman S . Demyelination in spinal cord injury. J Neurol Sci. 1989; 91(1-2):1-14. DOI: 10.1016/0022-510x(89)90072-5. View

20.

Zhang B, Arun G, Mao Y, Lazar Z, Hung G, Bhattacharjee G . The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep. 2012; 2(1):111-23. PMC: 3408587. DOI: 10.1016/j.celrep.2012.06.003. View