Global epigenomic reconfiguration during mammalian brain development. Academic Article uri icon

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.

published proceedings

  • Science

altmetric score

  • 210.506

author list (cited authors)

  • Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., ... Ecker, J. R.

citation count

  • 1367

complete list of authors

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

publication date

  • August 2013