Unlocking epigenetic codes in neurogenesis

Yao, Bing; Jin, Peng

doi:10.1101/gad.241547.114

Cited by 82 publications

(64 citation statements)

References 251 publications

(318 reference statements)

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“…Mouse phenotype enrichment analysis demonstrated that the defects in the down-regulated genes were almost exclusively associated with phenotypes such as abnormal learning/memory/conditioning and behavior, whereas those up-regulated were dominantly linked to defects in the development of non-neuronal tissues (Supplemental Fig. S3G,H The importance of long intergenic noncoding RNAs (lincRNAs) in neuronal development has been increasingly appreciated (Yao and Jin 2014). Our analysis further revealed that NMDA-driven neuronal activity also involves modulation of a large number of lincRNAs (Supplemental Fig.…”

Section: Nmda Receptor Activation Results In Massive Transcriptionalmentioning

confidence: 99%

Dynamics and function of distal regulatory elements during neurogenesis and neuroplasticity

et al. 2015

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Gene regulation in mammals involves a complex interplay between promoters and distal regulatory elements that function in concert to drive precise spatiotemporal gene expression programs. However, the dynamics of the distal gene regulatory landscape and its function in the transcriptional reprogramming that underlies neurogenesis and neuronal activity remain largely unknown. Here, we performed a combinatorial analysis of genome-wide data sets for chromatin accessibility (FAIREseq) and the enhancer mark H3K27ac, revealing the highly dynamic nature of distal gene regulation during neurogenesis, which gets progressively restricted to distinct genomic regions as neurons acquire a post-mitotic, terminally differentiated state. We further find that the distal accessible and active regions serve as target sites for distinct transcription factors that function in a stage-specific manner to contribute to the transcriptional program underlying neuronal commitment and maturation. Mature neurons respond to a sustained activity of NMDA receptors by epigenetic reprogramming at a large number of distal regulatory regions as well as dramatic reorganization of super-enhancers. Such massive remodeling of the distal regulatory landscape in turn results in a transcriptome that confers a transient loss of neuronal identity and gain of cellular plasticity. Furthermore, NMDA receptor activity also induces many novel prosurvival genes that function in neuroprotective pathways. Taken together, these findings reveal the dynamics of the distal regulatory landscape during neurogenesis and uncover novel regulatory elements that function in concert with epigenetic mechanisms and transcription factors to generate the transcriptome underlying neuronal development and activity.

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Section: Nmda Receptor Activation Results In Massive Transcriptionalmentioning

confidence: 99%

Dynamics and function of distal regulatory elements during neurogenesis and neuroplasticity

et al. 2015

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“…1). Genes from known modulators of adult neurogenesis include those involved in signaling transduction, vascular and immune system function, metabolic factors, and epigenetic regulation (Nho, Corneveaux et al 2013, Funa and Sasahara 2014, Urban and Guillemot 2014, Yao and Jin 2014, Borsini, Zunszain et al 2015). Pathway-based approaches were used to manually curate these hippocampal neurogenesis-related genes through a review of existing databases and literature mining, resulting in a final gene list (Fig.…”

Section: Methodsmentioning

confidence: 99%

Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease

Horgusluoglu‐Moloch

Nho

Risacher

et al. 2017

Neurobiology of Aging

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Alzheimer’s disease (AD) patients display hippocampal atrophy, memory impairment, and cognitive decline. New neurons are generated throughout adulthood in two regions of the brain implicated in AD, the dentate gyrus of the hippocampus and the sub-ventricular zone of the olfactory bulb. Disruption of this process contributes to neurodegenerative diseases including AD and many of the molecular players in AD are also modulators of adult neurogenesis. However, the genetic mechanisms underlying adult neurogenesis in AD have been underexplored. To address this gap, we performed a gene-based association analysis in cognitively normal and impaired participants using neurogenesis pathway-related candidate genes curated from existing databases, literature mining, and large-scale genome-wide association study findings. A gene-based association analysis identified ADORA2A as significantly associated with hippocampal volume and the association between rs9608282 within ADORA2A and hippocampal volume was replicated in the meta-analysis after multiple comparison adjustments (p=7.88×10−6). The minor allele of rs9608282 in ADORA2A is associated with larger hippocampal volumes and better memory.

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“…Recent studies have identified the critical role of miRNAs, which especially in the brain [124,125]. And their function in neurogenesis has been reviewed extensively in recent years [125][126][127][128][129][130]. For instance, microRNA-9 (miR-9) has been shown to decrease neural stem cell proliferation and facilitate neural differentiation by suppressing TLX expression [131].…”

Section: Ncrnas In Embryonic Neurogenesismentioning

confidence: 99%