RGD Reference Report - Potential role of estrogen in regulation of the insulin-like growth factor2-H19 locus in the rat testis. - Rat Genome Database

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Potential role of estrogen in regulation of the insulin-like growth factor2-H19 locus in the rat testis.

Authors: Pathak, S  D'Souza, R  Ankolkar, M  Gaonkar, R  Balasinor, NH 
Citation: Pathak S, etal., Mol Cell Endocrinol. 2010 Jan 15;314(1):110-7. doi: 10.1016/j.mce.2009.08.005. Epub 2009 Aug 14.
RGD ID: 8694315
Pubmed: PMID:19683557   (View Abstract at PubMed)
DOI: DOI:10.1016/j.mce.2009.08.005   (Journal Full-text)

The selective estrogen receptor modulator, tamoxifen, has been shown to reduce DNA methylation at Insulin-like growth factor 2/H19 differentially methylated region (Igf2/H19 DMR) in the spermatozoa of the Holtzman rats. Since imprint at this locus is acquired during spermatogenesis in the male germ-line, we hypothesized role for estrogen signaling in the methylation dynamics in the testis. The present study was designed to identify putative estrogen response elements (ERE) at Igf2/H19 DMR and their interaction with DNA methylation pathway. Here, we demonstrate presence of functional ERE at 2637/2655 base pair on Igf2/H19 DMR in testicular germ cells, which was found to bind to estrogen receptor beta (ER beta) in the chromatin immunoprecipitation assay. Tamoxifen attenuated ER beta-ERE association thereby acting as an estrogen antagonist at this locus. Further mechanistic study involving colocalization and immunoprecipitation assay revealed interaction of ER beta and Dnmt1 in the testis. The study provides evidence for the role for estrogen in acquisition of imprint at Igf2/H19 DMR in testis and help in understanding molecular mechanism of environmental estrogens impacting male fertility.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Dnmt1  (DNA methyltransferase 1)
Esr2  (estrogen receptor 2)
Pcna  (proliferating cell nuclear antigen)


Additional Information