scholarly journals Global Epigenomic Reconfiguration During Mammalian Brain Development

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 1237905 ◽  
Author(s):  
Ryan Lister ◽  
Eran A. Mukamel ◽  
Joseph R. Nery ◽  
Mark Urich ◽  
Clare A. Puddifoot ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Adult Development ◽  
Fetal Brain ◽  
Brain Cell ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dominant Form ◽  
Single Base ◽  
Single Base Resolution

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.

scholarly journals The Expression and Distributions of ANP32A in the Developing Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shanshan Wang ◽  
Yunliang Wang ◽  
Qingshan Lu ◽  
Xinshan Liu ◽  
Fuyu Wang ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Fetal Brain ◽  
Tissue Expression ◽  
Developing Brain ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dependent Manner ◽  
Growing Up ◽  
Embryonic Mouse ◽  
And Function

Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A (ANP32A), has multiple functions involved in neuritogenesis, transcriptional regulation, and apoptosis. However, whether ANP32A has an effect on the mammalian developing brain is still in question. In this study, it was shown that brain was the organ that expressed the most abundant ANP32A by human multiple tissue expression (MTE) array. The distribution of ANP32A in the different adult brain areas was diverse dramatically, with high expression in cerebellum, temporal lobe, and cerebral cortex and with low expression in pons, medulla oblongata, and spinal cord. The expression of ANP32A was higher in the adult brain than in the fetal brain of not only humans but also mice in a time-dependent manner. ANP32A signals were dispersed accordantly in embryonic mouse brain. However, ANP32A was abundant in the granular layer of the cerebellum and the cerebral cortex when the mice were growing up, as well as in the Purkinje cells of the cerebellum. The variation of expression levels and distribution of ANP32A in the developing brain would imply that ANP32A may play an important role in mammalian brain development, especially in the differentiation and function of neurons in the cerebellum and the cerebral cortex.

scholarly journals Bacterial Epigenomics: Coming of Age

mSystems ◽  
2021 ◽  
Author(s):  
Pedro H. Oliveira
Keyword(s):  
Dna Methylation ◽  
Coming Of Age ◽  
Innate Immune ◽  
Physiological Significance ◽  
Single Base ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Single Base Resolution

Epigenetic DNA methylation in bacteria has been traditionally studied in the context of antiparasitic defense and as part of the innate immune discrimination between self and nonself DNA. However, sequencing advances that allow genome-wide analysis of DNA methylation at the single-base resolution are nowadays expanding and have propelled a modern epigenomic revolution in our understanding of the extent, evolution, and physiological significance of methylation.

scholarly journals Secondary Zinc Deficiency via Exposure to the Environmental Toxicant Di-2-ethylhexyl phthalate Affects Neurogenesis at Embryonic Day 19

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1220-1220
Author(s):  
Xiuzhen Liu ◽  
Patricia Oteiza
Keyword(s):  
Brain Development ◽  
Zinc Deficiency ◽  
Zinc Concentration ◽  
Fetal Brain ◽  
Adult Brain ◽  
Acid Decarboxylase ◽  
Environmental Toxicants ◽  
Gestational Exposure ◽  
Marginal Zinc Deficiency ◽  
Ethylhexyl Phthalate

Abstract Objectives Zinc deficiency can affect early brain development. We previously found that developmental marginal zinc deficiency affected neurogenesis leading to a lower number of neurons and altered neural specification in the adult rat brain. Zinc deficiency can occur as low dietary zinc intake and secondary to diseases, infections, and exposure to environmental toxicants such as phthalates. This work investigated if gestational exposure to toxicant Di-2-ethylhexyl phthalate (DEHP) could decrease zinc availability to the fetus and altered neurogenesis. Methods Rats were fed an adequate (25 µg zinc/g diet) (C) or a marginal zinc deficient (MZD) (10 µg zinc/g diet), without or with DEHP (300 mg/kg BW) (C + DEHP, MZD + DEHP) from gestational day zero until embryonic day 19 (E19). Zinc concentration was analyzed by atomic absorption spectrometry (AAS). Neurogenesis was evaluated in the offspring at E19 measuring parameters of neural progenitor cells (NPC) proliferation and differentiation by Western blot and/or immunofluorescence. Results Fetal brain zinc concentration was significantly decreased in MZD, C + DEHP and MZD + DEHP than in C. Protein Markers of neurogenesis (NeuN, PAX6, SOX2, TBR2) were lower in MZD and C + DEHP than C, and lowest in MZD + DEHP. The excitatory neuron marker vesicular glutamate transporter 1 (VGLUT1) was lower in C + DEHP, MZD and MZD + DEHP than in C, while the marker of inhibitory neurons glutamic acid decarboxylase (GAD65) level were similar among groups. The ERK1/2 pathway, crucial to neurogenesis, was affected by MZD and DEHP. ERK1/2 activation was lower, and at a similar extent in C + DEHP and MZD groups than in C, while it was markedly lower in the MZD + DEHP group compared to all other groups. Lower ERK1/2 activation could be due to activation of the ERK1/2 phosphatase 2A (PP2A). We found that PP2A activation was higher, in MZD and DEHP than in C, being highest in the MZD + DEHP group. Conclusions Gestational exposure to DEHP in rats causes a secondary zinc deficiency in the fetal brain and altered neurogenesis. This can be due to the inhibition of the ERK1/2 signaling pathway. DEHP exposure can adversely affect the offspring's brain development and result in irreversible consequences to adult brain structure and function. Funding Sources Supported by grants from NIFA CA-D-XXX-7244-H, Packer-Wentz foundation, NIEHS T 32 training grant (T32 ES 0,07059).

scholarly journals Mammalian Brain Development is Accompanied by a Dramatic Increase in Bipolar DNA Methylation

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ming-an Sun ◽  
Zhixiong Sun ◽  
Xiaowei Wu ◽  
Veena Rajaram ◽  
David Keimig ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Mammalian Brain

scholarly journals DNA modifications in the mammalian brain

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130512 ◽  
Author(s):  
Jaehoon Shin ◽  
Guo-li Ming ◽  
Hongjun Song
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Genomic Imprinting ◽  
Mammalian Brain ◽  
Epigenetic Mark ◽  
Mammalian Development ◽  
Dna Modifications ◽  
Dna Elements ◽  
And Function ◽  
Neuronal Functions

DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function.

scholarly journals MethBank: a database integrating next-generation sequencing single-base-resolution DNA methylation programming data

2014 ◽  
Vol 43 (D1) ◽  
pp. D54-D58 ◽  
Author(s):  
Dong Zou ◽  
Shixiang Sun ◽  
Rujiao Li ◽  
Jiang Liu ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Single Base ◽  
Single Base Resolution ◽  
Generation Sequencing

scholarly journals EM-seq: Detection of DNA Methylation at Single Base Resolution from Picograms of DNA

2019 ◽  
Author(s):  
Romualdas Vaisvila ◽  
V. K. Chaithanya Ponnaluri ◽  
Zhiyi Sun ◽  
Bradley W. Langhorst ◽  
Lana Saleh ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bisulfite Sequencing ◽  
Nucleotide Composition ◽  
Whole Genome ◽  
Sequencing Data ◽  
Genomic Features ◽  
Single Base ◽  
Bisulfite Treatment ◽  
Genome Bisulfite Sequencing ◽  
Single Base Resolution

AbstractBisulfite sequencing is widely used to detect 5mC and 5hmC at single base resolution. However, bisulfite treatment damages DNA resulting in fragmentation, loss of DNA and biased sequencing data. To overcome this, we developed Enzymatic Methyl-seq (EM-seq), an enzymatic based approach that uses as little as 100 pg of DNA. EM-seq outperformed bisulfite converted libraries in all metrics examined including coverage, duplication, sensitivity and nucleotide composition. EM-seq libraries displayed even GC distribution, improved correlation across input amounts as well as increased representation of genomic features. These data indicate that EM-seq is more accurate and reliable than whole genome bisulfite sequencing (WGBS).

scholarly journals Novel Epigenetic Clock for Fetal Brain Development Predicts Fetal Epigenetic Age for iPSCs and iPSC-Derived Neurons.

2020 ◽  
Author(s):  
Leonard C Steg ◽  
Gemma L Shireby ◽  
Jennifer Imm ◽  
Jonathan P Davies ◽  
Robert Flynn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Fetal Brain ◽  
Cell Types ◽  
Biological Research ◽  
Epigenetic Clock ◽  
Cellular Model ◽  
Neuronal Precursor Cells ◽  
Age Related ◽  
Epigenetic Age

Abstract Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the early stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age, and is has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons, here, we establish the fetal brain clock (FBC), a bespoke epigenetic clock trained in prenatal neurodevelopmental samples. Our data show that the FBC outperforms other established epigenetic clocks in predicting the age of fetal brain samples. We then applied the FBC to DNA methylation data of cellular datasets that have profiled iPSCs and iPSC-derived neuronal precursor cells and neurons and find that these cell types are characterized by a fetal epigenetic age. Furthermore, while differentiation from iPSCs to neurons significantly increases the epigenetic age, iPSC-neurons are still predicted as having fetal epigenetic age. Together our findings reiterate the need for better understanding of the limitations of existing epigenetic clocks for answering biological research questions and highlight a potential limitation of iPSC-neurons as a cellular model for the research of age-related diseases as they might not fully recapitulate an aged phenotype.

Sign in / Sign up

Export Citation Format

Share Document