title: Exploring the potential relationship between Notch pathway genes expression and their promoter methylation in mice hippocampal neurogenesis.
abstract: The Notch pathway is a highly conserved pathway that regulates hippocampal neurogenesis during embryonic development and adulthood. It has become apparent that intracellular epigenetic modification including DNA methylation is deeply involved in fate specification of neural stem cells (NSCs). However, it is still unclear whether the Notch pathway regulates hippocampal neurogenesis by changing the Notch genes' DNA methylation status. Here, we present the evidence from DNA methylation profiling of Notch1, Hes1 and Ngn2 promoters during neurogenesis in the dentate gyrus (DG) of postnatal, adult and traumatic brains. We observed the expression of Notch1, Hes1 and Ngn2 in hippocampal DG with qPCR, Western blot and immunofluorescence staining. In addition, we investigated the methylation status of Notch pathway genes using the bisulfite sequencing PCR (BSP) method. The number of Notch1 or Hes1 (+) and BrdU (+) cells decreased in the subgranular zone (SGZ) of the DG in the hippocampus following TBI. Nevertheless, the number of Ngn2-positive cells in the DG of injured mice was markedly higher than in the DG of non-TBI mice. Accordingly, the DNA methylation level of the three gene promoters changed with their expression in the DG. These findings suggest that the strict spatio-temporal expression of Notch effector genes plays an important role during hippocampal neurogenesis and suggests the possibility that Notch1, Hes1 and Ngn2 were regulated by changing some specific CpG sites of their promoters to further orchestrate neurogenesis in vivo.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, PR China.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Baoding No. 1 Hospital, Baoding 071000, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Litong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Zhangning
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, Heji Hospital affiliated Changzhi Medical College, 271 Taihang East Road, Changzhi 046000, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Xinwang
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Heji Hospital affiliated Changzhi Medical College, 271 Taihang East Road, Changzhi 046000, PR China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Tianjin Neurological Institute, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, PR China. Electronic address: yangxinyu@tijmu.edu.cn.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D018891:Dentate Gyrus / Q000378:metabolism / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C102938:Neurog2 protein, mouse; C497762:Notch1 protein, mouse
keywords: DNA methylation; Hes1; Hippocampal neurogenesis; Neurogenin2; Notch1