Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 15220929

Epigenetic programming by maternal behavior.

Ian C G Weaver·Nadia Cervoni·Frances A Champagne·Ana C D'Alessio·Shakti Sharma·Jonathan R Seckl·Sergiy Dymov·Moshe Szyf·Michael J Meaney
View original source ↗Export metadata ↓

Abstract

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

Explore related subjects

AcetylationAnimalsBase SequenceBlotting, WesternDNA MethylationEnzyme InhibitorsEpigenesis, GeneticFemaleGene Expression RegulationGroomingHippocampusHistone DeacetylasesHistonesHypothalamo-Hypophyseal SystemInjections, IntraventricularMaternal BehaviorMolecular Sequence DataPituitary-Adrenal SystemPolymerase Chain ReactionPromoter Regions, GeneticRatsReceptors, GlucocorticoidRepressor ProteinsStress, PsychologicalJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ian C G Weaver, Nadia Cervoni, Frances A Champagne, Ana C D'Alessio, Shakti Sharma, Jonathan R Seckl, Sergiy Dymov, Moshe Szyf, Michael J Meaney. 2004-06-27. Epigenetic programming by maternal behavior.. https://doi.org/10.1038/nn1276

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2019

Increased acetylation of H3K14 in the genomic regions that encode trained immunity enzymes in lysophosphatidylcholine-activated human aortic endothelial cells - Novel qualification markers for chronic disease risk factors and conditional DAMPs.

To test our hypothesis that proatherogenic lysophosphatidylcholine (LPC) upregulates trained immunity pathways (TIPs) in human aortic endothelial cells (HAECs), we conducted an intensive analyses on our RNA-Seq data and histone 3 lysine 14 acetylation (H3K14ac)-CHIP-Seq data, both performed on HAEC treated with LPC. Our analysis revealed that: 1) LPC induces upregulation of three TIPs including glycolysis enzymes (GE), mevalonate enzymes (ME), and acetyl-CoA generating enzymes (ACE); 2) LPC induces upregulation of 29% of 31 histone acetyltransferases, three of which acetylate H3K14; 3) LPC induces H3K14 acetylation (H3K14ac) in the genomic DNA that encodes LPC-induced TIP genes (79%) in comparison to that of in LPC-induced effector genes (43%) including ICAM-1; 4) TIP pathways are significantly different from that of EC activation effectors including adhesion molecule ICAM-1; 5) reactive oxygen species generating enzyme NOX2 deficiency decreases, but antioxidant transcription factor Nrf2 deficiency increases, the expressions of a few TIP genes and EC activation effector genes; and 6) LPC induced TIP genes(81%) favor inter-chromosomal long-range interactions (CLRI, trans-chromatin interaction) while LPC induced effector genes (65%) favor intra-chromosomal CLRIs (cis-chromatin interaction). Our findings demonstrated that proatherogenic lipids upregulate TIPs in HAECs, which are a new category of qualification markers for chronic disease risk factors and conditional DAMPs and potential mechanisms for acute inflammation transition to chronic ones. These novel insights may lead to identifications of new cardiovascular risk factors in upregulating TIPs in cardiovascular cells and novel therapeutic targets for the treatment of metabolic cardiovascular diseases, inflammation, and cancers. (total words: 245).

Acetylation↗
PubMed2005

Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid.

Valproic acid (VA) is a well-tolerated drug used to treat seizure disorders and has recently been shown to inhibit histone deacetylase (HDAC). Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radioresponse, we investigated the effects of VA on the radiosensitivity of human brain tumor cells grown in vitro and in vivo. The human brain tumor cell lines SF539 and U251 were used in our study. Histone hyperacetylation served as an indicator of HDAC inhibition. The effects of VA on tumor cell radiosensitivity in vitro were assessed using a clonogenic survival assay and gammaH2AX expression was determined as a measure of radiation-induced DNA double strand breaks. The effect of VA on the in vivo radioresponse of brain tumor cells was evaluated according to tumor growth delay analysis carried out on U251 xenografts. Irradiation at the time of maximum VA-induced histone hyperacetylation resulted in significant increases in the radiosensitivity of both SF539 and U251 cells. The radiosensitization was accompanied by a prolonged expression of gammaH2AX. VA administration to mice resulted in a clearly detectable level of histone hyperacetylation in U251 xenografts. Irradiation of U251 tumors in mice treated with VA resulted in an increase in radiation-induced tumor growth delay. Valproic acid enhanced the radiosensitivity of both SF539 and U251 cell lines in vitro and U251 xenografts in vivo, which correlated with the induction of histone hyperacetylation. Moreover, the VA-mediated increase in radiation-induced cell killing seemed to involve the inhibition of DNA DSB repair.

Acetylation↗
PubMed2005

Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.

Protein acetyltransferases and deacetylases have been implicated in oncogenesis, apoptosis and cell cycle regulation. Most of the protein acetyltransferases described acetylate epsilon-amino groups of lysine residues within proteins. Mouse ARD1 (homologue of yeast Ard1p, where Ard1p stands for arrest defective 1 protein) is the only known protein acetyltransferase catalysing acetylation of proteins at both alpha-(N-terminus) and epsilon-amino groups. Yeast Ard1p interacts with Nat1p (N-acetyltransferase 1 protein) to form a functional NAT (N-acetyltransferase). We now describe the human homologue of Nat1p, NATH (NAT human), as the partner of the hARD1 (human ARD1) protein. Included in the characterization of the NATH and hARD1 proteins is the following: (i) endogenous NATH and hARD1 proteins are expressed in human epithelial, glioma and promyelocytic cell lines; (ii) NATH and hARD1 form a stable complex, as investigated by reciprocal immunoprecipitations followed by MS analysis; (iii) NATH-hARD1 complex expresses N-terminal acetylation activity; (iv) NATH and hARD1 interact with ribosomal subunits, indicating a co-translational acetyltransferase function; (v) NATH is localized in the cytoplasm, whereas hARD1 localizes both to the cytoplasm and nucleus; (vi) hARD1 partially co-localizes in nuclear spots with the transcription factor HIF-1alpha (hypoxia-inducible factor 1alpha), a known epsilon-amino substrate of ARD1; (vii) NATH and hARD1 are cleaved during apoptosis, resulting in a decreased NAT activity. This study identifies the human homologues of the yeast Ard1p and Nat1p proteins and presents new aspects of the NATH and hARD1 proteins relative to their yeast homologues.

Acetylation↗