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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...

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Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
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Complex modulation of androgen responsive gene expression by methoxyacetic acid.

Gargi Bagchi1, Yijing Zhang, Kerri A Stanley

  • 1Department of Biology, Boston University, Boston, MA 02215, USA.

Reproductive Biology and Endocrinology : RB&E
|April 2, 2011
PubMed
Summary

Methoxyacetic acid (MAA) impacts androgen-responsive genes in Leydig cells, affecting various cellular processes. This study reveals complex interactions between MAA, testosterone, and gene expression critical for testicular function.

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Area of Science:

  • Reproductive Biology
  • Endocrinology
  • Toxicology

Background:

  • Optimal androgen signaling is crucial for testicular development and spermatogenesis.
  • Methoxyacetic acid (MAA), a metabolite of ethylene glycol monomethyl ether, disrupts spermatogenesis and causes testicular atrophy.
  • Previous studies suggested MAA enhances androgen receptor activity, but in vivo effects on gene expression were unknown.

Purpose of the Study:

  • To investigate the in vivo effects of MAA on androgen-responsive gene expression.
  • To identify specific genes and pathways affected by MAA and testosterone interactions.
  • To understand the molecular mechanisms underlying MAA-induced testicular dysfunction.

Main Methods:

  • Utilized a mouse TM3 Leydig cell line stably expressing the androgen receptor (TM3-AR).
  • Performed transcriptional profiling to analyze global gene expression changes.
  • Conducted motif analysis to identify enriched transcription factor binding sites.

Main Results:

  • MAA demonstrated widespread effects on androgen-responsive genes, influencing apoptosis, ion transport, cell adhesion, phosphorylation, and transcription.
  • MAA could both enhance and antagonize androgenic responses.
  • Testosterone modulated MAA's effects, showing both positive and negative influences.
  • FOXO targets, including developmental genes and Hox genes, were significantly affected by the interplay of testosterone and MAA.

Conclusions:

  • The study highlights intricate interactions between testosterone and MAA in Leydig cells.
  • Findings provide insights into how MAA exposure impacts androgen-dependent processes.
  • This research contributes to understanding the molecular basis of MAA's toxicity on male reproductive health.