Global epigenomic reconfiguration during mammalian brain development

Ryan Lister; Eran A. Mukamel; Joseph R. Nery; Mark Urich; Clare A. Puddifoot; Nicholas D. Johnson; Jacinta Lucero; Yun Huang; Andrew J. Dwork; Matthew D. Schultz; Miao Yu; Julian Tonti-Filippini; Holger Heyn; Shijun Hu; Joseph C. Wu; Anjana Rao; Manel Esteller; Chuan He; Fatemeh G. Haghighi; Terrence J. Sejnowski; M. Margarita Behrens; Joseph R. Ecker

doi:10.1126/science.1237905

Global epigenomic reconfiguration during mammalian brain development

Ryan Lister, Eran A. Mukamel, Joseph R. Nery, Mark Urich, Clare A. Puddifoot, Nicholas D. Johnson, Jacinta Lucero, Yun Huang, Andrew J. Dwork, Matthew D. Schultz, Miao Yu, Julian Tonti-Filippini, Holger Heyn, Shijun Hu, Joseph C. Wu, Anjana Rao, Manel Esteller, Chuan He, Fatemeh G. Haghighi, Terrence J. SejnowskiM. Margarita Behrens, Joseph R. Ecker

Research output: Contribution to journal › Article › peer-review

1491 Scopus citations

Abstract

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.

Original language	English
Article number	1237905
Journal	Science
Volume	341
Issue number	6146
DOIs	https://doi.org/10.1126/science.1237905
State	Published - 2013
Externally published	Yes

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Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., Yu, M., Tonti-Filippini, J., Heyn, H., Hu, S., Wu, J. C., Rao, A., Esteller, M., He, C., Haghighi, F. G., ... Ecker, J. R. (2013). Global epigenomic reconfiguration during mammalian brain development. Science, 341(6146), Article 1237905. https://doi.org/10.1126/science.1237905

@article{f7584e41620e4e9180b7868b7158b12c,

title = "Global epigenomic reconfiguration during mammalian brain development",

abstract = "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.",

author = "Ryan Lister and Mukamel, {Eran A.} and Nery, {Joseph R.} and Mark Urich and Puddifoot, {Clare A.} and Johnson, {Nicholas D.} and Jacinta Lucero and Yun Huang and Dwork, {Andrew J.} and Schultz, {Matthew D.} and Miao Yu and Julian Tonti-Filippini and Holger Heyn and Shijun Hu and Wu, {Joseph C.} and Anjana Rao and Manel Esteller and Chuan He and Haghighi, {Fatemeh G.} and Sejnowski, {Terrence J.} and Behrens, {M. Margarita} and Ecker, {Joseph R.}",

year = "2013",

doi = "10.1126/science.1237905",

language = "English",

volume = "341",

journal = "Science",

issn = "0036-8075",

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number = "6146",

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Lister, R, Mukamel, EA, Nery, JR, Urich, M, Puddifoot, CA, Johnson, ND, Lucero, J, Huang, Y, Dwork, AJ, Schultz, MD, Yu, M, Tonti-Filippini, J, Heyn, H, Hu, S, Wu, JC, Rao, A, Esteller, M, He, C, Haghighi, FG, Sejnowski, TJ, Behrens, MM & Ecker, JR 2013, 'Global epigenomic reconfiguration during mammalian brain development', Science, vol. 341, no. 6146, 1237905. https://doi.org/10.1126/science.1237905

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T1 - Global epigenomic reconfiguration during mammalian brain development

AU - Lister, Ryan

AU - Mukamel, Eran A.

AU - Nery, Joseph R.

AU - Urich, Mark

AU - Puddifoot, Clare A.

AU - Johnson, Nicholas D.

AU - Lucero, Jacinta

AU - Huang, Yun

AU - Dwork, Andrew J.

AU - Schultz, Matthew D.

AU - Yu, Miao

AU - Tonti-Filippini, Julian

AU - Heyn, Holger

AU - Hu, Shijun

AU - Wu, Joseph C.

AU - Rao, Anjana

AU - Esteller, Manel

AU - He, Chuan

AU - Haghighi, Fatemeh G.

AU - Sejnowski, Terrence J.

AU - Behrens, M. Margarita

AU - Ecker, Joseph R.

PY - 2013

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N2 - 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.

AB - 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.

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SN - 0036-8075

VL - 341

JO - Science

JF - Science

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ER -

Global epigenomic reconfiguration during mammalian brain development

Abstract

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