AP2alpha and AP2gamma: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs

McPherson, Lisa; Weigel, Ronald J.

doi:10.1093/nar/27.20.4040

Cited by 102 publications

(88 citation statements)

References 27 publications

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“…There is evidence that the activity of each of these transcription factors is affected by the presence or absence of DNA methylation (3,(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). For some of these transcription factors, the databases contained multiple identical position weight matrices.…”

Section: Methodsmentioning

confidence: 99%

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

Suderman

McGowan

Sasaki

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

284

186

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Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCOR-TICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience.conservation | neuronal plasticity V ariation in early life experience is associated with differences in life-long health and behavioral trajectories in animals as well as humans. For example, differences in maternal care in rats during the first week of life are associated with long-term effects on behavior and brain function that persist into adulthood, including alterations in the stress response (1). In humans, similar effects are observed. For instance, childhood maltreatment associates with development of both externalizing and internalizing personality traits and psychopathology in adulthood (2). The association in both rats and humans of stable developmental phenotypes with early life experience suggests that molecular mechanisms may serve as a memory of these early life experiences in both species. In fact, there is evidence that these long-term effects are, at least in part, mediated by epigenetic alterations in the brain. In particular, recent studies have found aberrant DNA methylation in the NR3C1 (GLUCOCORTICOID RECEPTOR) gene promoter of the hippocampi of both rats and humans associated with differential early life experience (3, 4). Exposure of infant rats to stressed caretakers displaying abusive behavior produced persisting changes in methylation of the BDNF gene promoter in the adult prefrontal cortex (5). Early life stress in mice caused sustained DNA hypomethylation of an important regulatory region of the AVP gene (6).Although explanations involving a single site are appealing, it is unlikely that the broad systemic response to early life experien...

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Section: Methodsmentioning

confidence: 99%

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

Suderman

McGowan

Sasaki

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

284

186

View full text Add to dashboard Cite

show abstract

“…The AP-2␤ expression plasmid RSVNco␤ was provided by Dr. Helen Hurst (15). The AP-2␥ expression vector AP-2␥-pcDNA3 was provided by Dr. Ronald J. Weigel (32). The human AP-2B expression plasmid pSG5-AP-2B was provided by Dr. Michael A. Tainsky (33).…”

Section: Methodsmentioning

confidence: 99%

A Family of AP-2 Proteins Down-regulate Manganese Superoxide Dismutase Expression

Zhu¹,

Huang²,

Oberley

et al. 2001

Journal of Biological Chemistry

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“…The AP-2g expression vector AP-2g-pcDNA3 was generously provided by Dr Ronald J Weigel (McPherson and Weigel, 1999). Both Ad-AP-2a and Ad-AP-2g adenoviruses were manufactured at the University of Iowa's Gene Transfer Vector Core Facility.…”

Section: Cell Culturementioning

confidence: 99%

AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells

Watts

Oshiro

et al. 2006

Oncogene

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Activating enhancer-binding protein 2a (AP-2a) and activating enhancer-binding protein 2c (AP-2c) are transcription factors that bind GC-rich consensus sequences and regulate the expression of many downstream genes. AP-2a and AP-2c interact with p53 both physically and functionally. Expression microarray results in human breast carcinoma cells with forced p53 expression revealed AP-2c as a putative transcriptional target of p53. To confirm and extend these findings we measured the effects of forced p53 expression in human breast carcinoma cells by real-time reverse transcription-PCR, Western blotting, electrophoretic gel mobility shift assays, promoter reporter, chromatin immunoprecipitation and chromatin accessibility assays. Wild-type p53 expression rapidly induced not only AP-2c but also AP-2a mRNA. The subsequent increase in these proteins led to increased AP-2 DNAbinding and transactivating activity. Candidate p53-binding sites were identified in the AP-2a and AP-2c promoters. p53 binding to these cis-elements in vivo was also observed, together with a relaxation of chromatin structure in these regions. Finally, expression of either AP-2a or c inhibited growth of human breast carcinoma cells in vitro. Taken together, our findings indicate that these AP-2 genes are targets for transcriptional activation by p53 and suggest that AP-2 proteins may mediate some of the downstream effects of p53 expression such as inhibition of proliferation.

show abstract

AP2alpha and AP2gamma: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs

Cited by 102 publications

References 27 publications

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

A Family of AP-2 Proteins Down-regulate Manganese Superoxide Dismutase Expression

AP-2α and AP-2γ are transcriptional targets of p53 in human breast carcinoma cells

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