title: Immune Regulator MCPIP1 Modulates TET Expression during Early Neocortical Development.
abstract: MCPIP1 is a recently identified immune regulator that plays critical roles in preventing immune disorders, and is also present in the brain. Currently an unresolved question remains as to how MCPIP1 performs its non-immune functions in normal brain development. Here, we report that MCPIP1 is abundant in neural progenitor cells (NPCs) and newborn neurons during the early stages of neurogenesis. The suppression of MCPIP1 expression impairs normal neuronal differentiation, cell-cycle exit, and concomitant NPC proliferation. MCPIP1 is important for maintenance of the NPC pool. Notably, we demonstrate that MCPIP1 reduces TET (TET1/TET2/TET3) levels and then decreases 5-hydroxymethylcytosine levels. Furthermore, the MCPIP1 interaction with TETs is involved in neurogenesis and in establishing the proper number of NPCs in vivo. Collectively, our findings not only demonstrate that MCPIP1 plays an important role in early cortical neurogenesis but also reveal an unexpected link between neocortical development, immune regulators, and epigenetic modification.
authors: State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Huihui
authors: H
authors: Jiang
authors: State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Xiaohui
authors: X
authors: Lv
authors: State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Xuepei
authors: X
authors: Lei
authors: Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Ying
authors: Y
authors: Yang
authors: Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Xin
authors: X
authors: Yang
authors: State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: jwjiao@ioz.ac.cn.
authors: Jianwei
authors: J
authors: Jiao
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics; D019175:DNA Methylation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D019579:Neocortex / Q000196:embryology* / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D059372:Nucleotide Motifs; D038081:Organogenesis / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D012260:Ribonucleases; C541320:Zc3h12a protein, mouse