Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells

Matilde Marchi, Alessia Guarda, Anna Bergo, Nicoletta Landsberger, Charlotte Kilstrup-Nielsen, Gian Michele Ratto, Mario Costa

Research output: Contribution to journalArticle

Abstract

MECP2 is an X-linked gene coding for a protein functioning as a transcriptional repressor. The protein MeCP2 (Methyl CpG-binding protein) is an abundant component of pericentric heterochromatin and its mutations or duplications are present in around 80% of patients with a neurological disorder known as Rett Syndrome. Although MeCP2 action depends critically on its binding to chromatin, very little is known about the dynamics of this process. Using fluorescence recovery after photobleaching in controlled conditions of protein concentration, we demonstrated that most of the GFP-MeCP2 fusion protein associates strongly and reversibly to pericentric heterocromatin whereas the remaining fraction is bound irreversibly. The mobility of the methyl-binding protein is influenced by the differentiation state of the host cells. Furthermore, residues downstream of the methyl-binding domain are critical for the interaction with chromatin. Whereas the binding is stabilised by the central region it is likely modulated by the most C-terminal region. Importantly, these residues are missing in several disease causing mutations. Our data suggest that alterations in the affinity of MeCP2 for chromatin might contribute to the pathological effects of mutations causing Rett Syndrome.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalEpigenetics
Volume2
Issue number3
Publication statusPublished - Jul 2007

Fingerprint

Methyl-CpG-Binding Protein 2
Chromatin
Rett Syndrome
Mutation
Carrier Proteins
Fluorescence Recovery After Photobleaching
X-Linked Genes
Heterochromatin
Nervous System Diseases
Proteins

Keywords

  • Chromatin
  • Epigenetics
  • Imaging
  • MeCP2
  • Rett Syndrome

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Marchi, M., Guarda, A., Bergo, A., Landsberger, N., Kilstrup-Nielsen, C., Ratto, G. M., & Costa, M. (2007). Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells. Epigenetics, 2(3), 187-197.

Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells. / Marchi, Matilde; Guarda, Alessia; Bergo, Anna; Landsberger, Nicoletta; Kilstrup-Nielsen, Charlotte; Ratto, Gian Michele; Costa, Mario.

In: Epigenetics, Vol. 2, No. 3, 07.2007, p. 187-197.

Research output: Contribution to journalArticle

Marchi, M, Guarda, A, Bergo, A, Landsberger, N, Kilstrup-Nielsen, C, Ratto, GM & Costa, M 2007, 'Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells', Epigenetics, vol. 2, no. 3, pp. 187-197.
Marchi M, Guarda A, Bergo A, Landsberger N, Kilstrup-Nielsen C, Ratto GM et al. Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells. Epigenetics. 2007 Jul;2(3):187-197.
Marchi, Matilde ; Guarda, Alessia ; Bergo, Anna ; Landsberger, Nicoletta ; Kilstrup-Nielsen, Charlotte ; Ratto, Gian Michele ; Costa, Mario. / Spatio-temporal dynamics and localization of MeCP2 and pathological mutants in living cells. In: Epigenetics. 2007 ; Vol. 2, No. 3. pp. 187-197.
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