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Huntington Disease l: Introduction

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show...

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Updated: May 7, 2026

An Electrochemiluminescence-Based Assay for MeCP2 Protein Variants

An Electrochemiluminescence-Based Assay for MeCP2 Protein Variants

Published on: May 22, 2020

MeCP2: a novel Huntingtin interactor.

Karen N McFarland¹, Megan N Huizenga, Shayna B Darnell

¹Department of Neurology and The McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.

Human Molecular Genetics

|October 10, 2013

Summary

Huntington's disease (HD) involves gene regulation issues. Mutant huntingtin (Htt) protein interacts with MeCP2, increasing its binding to the BDNF gene promoter and causing downregulation, a key finding for HD pathology.

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Published on: February 27, 2018

Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

Transcriptional dysregulation is implicated in Huntington's disease (HD) pathology.
The precise mechanisms causing selective gene downregulation in HD are not fully understood.
Mutant huntingtin (Htt) protein is known to interact with transcription factors, affecting gene expression.

Purpose of the Study:

To investigate the interaction between mutant huntingtin (Htt) and methyl-CpG binding protein 2 (MeCP2) in HD.
To elucidate the role of MeCP2 in the downregulation of target genes, such as BDNF, in HD.

Main Methods:

Utilized complementary biochemical approaches and Fluorescent Lifetime Imaging to measure Förster Resonance Energy Transfer (FRET).
Studied interactions in mouse and cellular models of HD.
Employed siRNA to decrease MeCP2 levels in mutant Htt-expressing cells.

Main Results:

Demonstrated direct interaction between Htt and MeCP2 in HD models.
Observed enhanced Htt-MeCP2 interaction with expanded polyglutamine (polyQ) tracts, particularly in the nucleus.
Found increased MeCP2 binding to the BDNF gene promoter in the presence of mutant Htt.
Showed that decreasing MeCP2 levels via siRNA restored BDNF levels in HD cells.

Conclusions:

Aberrant interactions between Htt and MeCP2 contribute to transcriptional dysregulation in HD.
MeCP2 plays a role in the downregulation of BDNF expression in the context of HD.
Targeting the Htt-MeCP2 interaction may offer therapeutic strategies for HD.