Tissue specific epigenetic differences in CRH gene expression

Abstract

Corticotropin Releasing Hormone (CRH), a 41-amino acid peptide, is a major regulator of hypothalamic-pituitary-adrenal axis function. CRH also has important roles in several processes pertaining to pregnancy and parturition, including being a possible regulator of gestational length and predictor of pre-term birth. Regulation of the CRH promoter exhibits some tissue-specificities, the most well characterized example being glucocorticoids, which can stimulate placental CRH production but suppress hypothalamic CRH. In the last decade there has been growing interest in the role of epigenetic regulation of gene expression. Modification of the structure of chromatin is an example of epigenetic change affecting gene expression. We have found that inhibition of histone deacetylases results in an increase in CRH expression in the AtT20 pituitary cell line, but a decrease in CRH expression in the placenta. In this paper we review tissue specific differences in CRH gene expression, and discuss how epigenetic chromatin modification mechanisms can relate to tissue specific differences in expression of CRH.

Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development

“…CRH protein is expressed throughout the brain (Abou-Seif et al, 2012) but is enriched in the hypothalamus and hippocampus where it plays a role in negative feedback control. CRH levels were assessed in the brain post nuclear lysate at E14 and E18.…”

Transgenerational transmission of pregestational and prenatal experience: maternal adversity, enrichment, and underlying epigenetic and environmental mechanisms

“…60,61 Considering CRH and glucocorticoids are implicated in an arousal pathway involving exaggerated anticipation of negative events, it follows that the upward regulation of CRH in the placenta is linked with the pathogenesis of chronic anxiety, fear and heightened vigilance in offspring. 60 In addition, CRH facilitates parturition and conditions of duress can cause glucocorticoids to prematurely elevate CRH levels in the placenta, increasing vulnerability to preterm delivery. 62,63 Preterm birth may serve to 'rescue' the fetus from an adverse environment or reduce the allocation of resources to a pregnancy occurring during stressful circumstances.…”

“…Epigenetic regulation of CRH and other information molecules has been detected in placental tissue 60 61 Considering CRH and glucocorticoids are implicated in an arousal pathway involving exaggerated anticipation of negative events, it follows that the upward regulation of CRH in the placenta is linked with the pathogenesis of chronic anxiety, fear and heightened vigilance in offspring 60 . In addition, CRH facilitates parturition and conditions of duress can cause glucocorticoids to prematurely elevate CRH levels in the placenta, increasing vulnerability to preterm delivery 62 …”

“…Epigenetic regulation of CRH and other information molecules has been detected in placental tissue 60 61 Considering CRH and glucocorticoids are implicated in an arousal pathway involving exaggerated anticipation of negative events, it follows that the upward regulation of CRH in the placenta is linked with the pathogenesis of chronic anxiety, fear and heightened vigilance in offspring 60 .…”

How has the Study of the Human Placenta Aided Our Understanding of Partially Methylated Genes?

“…Placental HMDs are enriched for genes involved in the defense response [28] and include α-defensins, α-interferons, selectins-E and -P, chemokine receptors, chemokine ligands and interleukins. Many of the genes in placental HMDs are important for normal pregnancy: low levels of IR1RN are associated with pre-eclampsia, high levels of THBD are associated with preterm birth [42,43], and CRH is a marker for the length of gestation and the timing of parturition [44]. Other genes are important for placental development and structure, including CCR1 , CCR2 , CCR3 and CCL14 , which are thought to be involved in trophoblast migration [45] and the desmosome genes, which are involved in cell–cell adhesion in the placenta [46].…”