@article{2976dab5230547188c80883924cc541c,
title = "Early-Life Gene Expression in Neurons Modulates Lasting Epigenetic States",
abstract = "In mammals, the environment plays a critical role in promoting the final steps in neuronal development during the early postnatal period. While epigenetic factors are thought to contribute to this process, the underlying molecular mechanisms remain poorly understood. Here, we show that in the brain during early life, the DNA methyltransferase DNMT3A transiently binds across transcribed regions of lowly expressed genes, and its binding specifies the pattern of DNA methylation at CA sequences (mCA) within these genes. We find that DNMT3A occupancy and mCA deposition within the transcribed regions of genes is negatively regulated by gene transcription and may be modified by early-life experience. Once deposited, mCA is bound by the methyl-DNA-binding protein MECP2 and functions in a rheostat-like manner to fine-tune the cell-type-specific transcription of genes that are critical for brain function. The deposition of repressive mCA marks by the methyltransferase DNMT3A across specific brain genes during early postnatal life is important for their regulation throughout life.",
author = "Hume Stroud and Su, {Susan C.} and Sinisa Hrvatin and Greben, {Alexander W.} and William Renthal and Boxer, {Lisa D.} and Nagy, {M. Aurel} and Hochbaum, {Daniel R.} and Benyam Kinde and Gabel, {Harrison W.} and Greenberg, {Michael E.}",
note = "Funding Information: We thank J. Nathans and A. Mo for SUN1 mice and E. Griffith, E. Pollina, and T. Cherry for editorial assistance; P. Zhang, J. Wang, and K. Fazioli for assistance with the mouse colony; and G. Mandel, A. Bird, and M. Morselli for helpful discussions. This work was supported by grants from the Rett Syndrome Research Trust and the NIH ( RO1NS048276 ) to M.E.G. and the NARSAD and Hearst funds to H.S. S.C.S. was supported by the NRSA training grant and fellowship ( T32NS007484 and F32NS089186 ). H.S. is an HHMI Fellow of the Damon Runyon Cancer Research Foundation ( DRG-2194-14 ). Funding Information: We thank J. Nathans and A. Mo for SUN1 mice and E. Griffith, E. Pollina, and T. Cherry for editorial assistance; P. Zhang, J. Wang, and K. Fazioli for assistance with the mouse colony; and G. Mandel, A. Bird, and M. Morselli for helpful discussions. This work was supported by grants from the Rett Syndrome Research Trust and the NIH (RO1NS048276) to M.E.G. and the NARSAD and Hearst funds to H.S. S.C.S. was supported by the NRSA training grant and fellowship (T32NS007484 and F32NS089186). H.S. is an HHMI Fellow of the Damon Runyon Cancer Research Foundation (DRG-2194-14). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = nov,
day = "16",
doi = "10.1016/j.cell.2017.09.047",
language = "English (US)",
volume = "171",
pages = "1151--1164.e16",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}