QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 14, 2007, 27(7):1756-1768; doi:10.1523/JNEUROSCI.4164-06.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (51) Citing Articles via Google Scholar Google Scholar Articles by Weaver, I. C. G. Articles by Meaney, M. J. Search for Related Content PubMed PubMed Citation Articles by Weaver, I. C. G. Articles by Meaney, M. J.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes

Ian C. G. Weaver,^1,2 Ana C. D'Alessio,³ Shelley E. Brown,³ Ian C. Hellstrom,¹ Sergiy Dymov,² Shakti Sharma,¹ Moshe Szyf,^2,3 and Michael J. Meaney^1,2

¹Douglas Hospital Research Center, Montréal, Québec, Canada H4H 1R3, and ²McGill Program for the Study of Behaviour, Genes, and Environment and ³Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada H3G 1Y6

Correspondence should be addressed to either of the following: Michael Meaney, Douglas Hospital Research Centre, 6875 LaSalle Boulevard, Montréal, Québec, Canada H4H 1R3, Email: michael.meaney{at}mcgill.ca; or Moshe Szyf, Department of Pharmacology, McGill University, 3655 Drummond Street, Montréal, Québec, Canada H3G 1Y6, Email: moshe.szyf{at}mcgill.ca

Maternal care alters epigenetic programming of glucocorticoid receptor (GR) gene expression in the hippocampus, and increased postnatal maternal licking/grooming (LG) behavior enhances nerve growth factor-inducible protein A (NGFI-A) transcription factor binding to the exon 1₇ GR promoter within the hippocampus of the offspring. We tested the hypothesis that NGFI-A binding to the exon 1₇ GR promoter sequence marks this sequence for histone acetylation and DNA demethylation and that such epigenetic alterations subsequently influence NGFI-A binding and GR transcription. We report that (1) NGFI-A binding to its consensus sequence is inhibited by DNA methylation, (2) NGFI-A induces the activity of exon 1₇ GR promoter in a transient reporter assay, (3) DNA methylation inhibits exon 1₇ GR promoter activity, and (4) whereas NGFI-A interaction with the methylated exon 1₇ GR promoter is reduced, NGFI-A overexpression induces histone acetylation, DNA demethylation, and activation of the exon 1₇ GR promoter in transient transfection assays. Site-directed mutagenesis assays demonstrate that NGFI-A binding to the exon 1₇ GR promoter is required for such epigenetic reprogramming. In vivo, enhanced maternal LG is associated with increased NGFI-A binding to the exon 1₇ GR promoter in the hippocampus of pups, and NGFI-A-bound exon 1₇ GR promoter is unmethylated compared with unbound exon 1₇ GR promoter. Knockdown experiments of NGFI-A in hippocampal primary cell culture show that NGFI-A is required for serotonin-induced DNA demethylation and increased exon 1₇ GR promoter expression. The data are consistent with the hypothesis that NGFI-A participates in epigenetic programming of GR expression.

Key words: maternal behavior; rat; hippocampus; transcription factors; glucocorticoid receptor; DNA methylation

---

Received Sept. 22, 2006; revised Dec. 18, 2006; accepted Jan. 8, 2007.

Correspondence should be addressed to either of the following: Michael Meaney, Douglas Hospital Research Centre, 6875 LaSalle Boulevard, Montréal, Québec, Canada H4H 1R3, Email: michael.meaney{at}mcgill.ca; or Moshe Szyf, Department of Pharmacology, McGill University, 3655 Drummond Street, Montréal, Québec, Canada H3G 1Y6, Email: moshe.szyf{at}mcgill.ca

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2007 27: i. [Full Text]  

This article has been cited by other articles:

				D. Noble Could there be a Synthesis between Western and Oriental Medicine, and with Sasang Constitutional Medicine in Particular? Evid. Based Complement. Altern. Med., September 1, 2009; 6(suppl_1): 5 - 10. [Abstract] [Full Text] [PDF]

				R. Lister and J. R. Ecker Finding the fifth base: Genome-wide sequencing of cytosine methylation Genome Res., June 1, 2009; 19(6): 959 - 966. [Abstract] [Full Text] [PDF]

				A. Guzzetta, S. Baldini, A. Bancale, L. Baroncelli, F. Ciucci, P. Ghirri, E. Putignano, A. Sale, A. Viegi, N. Berardi, et al. Massage Accelerates Brain Development and the Maturation of Visual Function J. Neurosci., May 6, 2009; 29(18): 6042 - 6051. [Abstract] [Full Text] [PDF]

				J. Bassingthwaighte, P. Hunter, and D. Noble The Cardiac Physiome: perspectives for the future Exp Physiol, May 1, 2009; 94(5): 597 - 605. [Abstract] [Full Text] [PDF]

				I. M Goodyer, T. Croudace, V. Dunn, J. Herbert, and P. B Jones Cohort Profile: Risk patterns and processes for psychopathology emerging during adolescence: the ROOTS project Int. J. Epidemiol., April 8, 2009; (2009) dyp173v1. [Full Text] [PDF]

				A. Kasneci, N. M. Kemeny-Suss, S. V. Komarova, and L. E. Chalifour Egr-1 negatively regulates calsequestrin expression and calcium dynamics in ventricular cells Cardiovasc Res, March 1, 2009; 81(4): 695 - 702. [Abstract] [Full Text] [PDF]

				E. Hara, L. Kubikova, N. A Hessler, and E. D Jarvis Assessing visual requirements for social context-dependent activation of the songbird song system Proc R Soc B, January 22, 2009; 276(1655): 279 - 289. [Abstract] [Full Text] [PDF]

				F. Hu, E. J. Crespi, and R. J. Denver Programming Neuroendocrine Stress Axis Activity by Exposure to Glucocorticoids during Postembryonic Development of the Frog, Xenopus laevis Endocrinology, November 1, 2008; 149(11): 5470 - 5481. [Abstract] [Full Text] [PDF]

				M. Szyf The Dynamic Epigenome and its Implications in Toxicology Toxicol. Sci., November 1, 2007; 100(1): 7 - 23. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help