Publications by authors named "P Melamed"

Objective: High concentrations of dehydroepiandrosterone sulfate (DHEAS) often precede premature puberty and sometimes polycystic ovary syndrome (PCOS). We hypothesized that the underlying mechanisms might involve DNA methylation. As an indicator of the downstream effects of DHEAS, we looked for associations between prepubertal DHEAS concentration, pubertal progression, and DNA methylation at puberty-related genes in blood cells.

View Article and Find Full Text PDF

Mammalian genomes contain thousands of genes for long noncoding RNA (lncRNAs), some of which have been shown to affect protein coding gene expression through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced, and polyadenylated, but not translated into protein. Nuclear lncRNAs can modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins.

View Article and Find Full Text PDF

Genome-wide studies have demonstrated regulatory roles for diverse non-coding elements, but their precise and interrelated functions have often remained enigmatic. Addressing the need for mechanistic insight, we studied their roles in expression of Lhb which encodes the pituitary gonadotropic hormone that controls reproduction. We identified a bi-directional enhancer in gonadotrope-specific open chromatin, whose functional eRNA (eRNA2) supports permissive chromatin at the Lhb locus.

View Article and Find Full Text PDF

Background: Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts.

View Article and Find Full Text PDF

5α-reductase-1 catalyzes production of various steroids, including neurosteroids. We reported previously that expression of its encoding gene, drops in murine ovaries and hypothalamic preoptic area (POA) after early-life immune stress, seemingly contributing to delayed puberty and ovarian follicle depletion, and in the ovaries the first intron was more methylated at two CpGs. Here, we hypothesized that this CpG-containing locus comprises a methylation-sensitive transcriptional enhancer for .

View Article and Find Full Text PDF