Ube3a/E6AP is involved in a subset of MeCP2 functions

Soeun Kim, Maria Chahrour, Shay Ben-Shachar, Janghoo Lim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that share many clinical features. The disease-causing mutations have been identified for both syndromes. Mutations in Methyl-CpG Binding Protein 2 (MECP2) are found in a majority of patients with classical RTT while absence of maternal allele or intragenic mutation in the maternal copy of UBE3A gene encoding the human papilloma virus E6-associated protein (E6AP) cause most cases of AS. Extensive studies have been performed to determine the cause of the neurological problems in each disease. However, the genetic and molecular basis of the overlap in phenotypes between RTT and AS remains largely unknown. Here we present evidence that the phenotypic similarities between the two syndromes might be due to the shared molecular functions between MeCP2 and E6AP in gene expression. Our genetic and biochemical studies suggest that E6AP acts as an essential cofactor for a subset of MeCP2 functions. Specifically, decreased expression of Ube3a was able to rescue the cellular phenotypes induced by MECP2-overexpression in Drosophila. And biochemical assays using mice and cell culture systems show that MeCP2 and E6AP physically interact and regulate the expression of shared target genes. Together these data suggest that MeCP2 and E6AP play a role in the transcriptional control of common target gene expression and provide some insight into why RTT and AS share several neurological phenotypes.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume437
Issue number1
DOIs
StatePublished - Jul 19 2013

Fingerprint

Angelman Syndrome
Rett Syndrome
Set theory
Methyl-CpG-Binding Protein 2
Proteins
Phenotype
Gene expression
Papillomaviridae
Mutation
Molecular Biology
Mothers
Gene Expression
Gene encoding
Nervous System Diseases
Viruses
Cell culture
Genes
Drosophila
Assays
Cell Culture Techniques

Keywords

  • Angelman syndrome
  • MeCP2
  • Rett syndrome
  • Ube3a/E6AP

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Ube3a/E6AP is involved in a subset of MeCP2 functions. / Kim, Soeun; Chahrour, Maria; Ben-Shachar, Shay; Lim, Janghoo.

In: Biochemical and Biophysical Research Communications, Vol. 437, No. 1, 19.07.2013, p. 67-73.

Research output: Contribution to journalArticle

Kim, Soeun ; Chahrour, Maria ; Ben-Shachar, Shay ; Lim, Janghoo. / Ube3a/E6AP is involved in a subset of MeCP2 functions. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 437, No. 1. pp. 67-73.
@article{1775cc06bdae4256aaa63d20db46bb75,
title = "Ube3a/E6AP is involved in a subset of MeCP2 functions",
abstract = "Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that share many clinical features. The disease-causing mutations have been identified for both syndromes. Mutations in Methyl-CpG Binding Protein 2 (MECP2) are found in a majority of patients with classical RTT while absence of maternal allele or intragenic mutation in the maternal copy of UBE3A gene encoding the human papilloma virus E6-associated protein (E6AP) cause most cases of AS. Extensive studies have been performed to determine the cause of the neurological problems in each disease. However, the genetic and molecular basis of the overlap in phenotypes between RTT and AS remains largely unknown. Here we present evidence that the phenotypic similarities between the two syndromes might be due to the shared molecular functions between MeCP2 and E6AP in gene expression. Our genetic and biochemical studies suggest that E6AP acts as an essential cofactor for a subset of MeCP2 functions. Specifically, decreased expression of Ube3a was able to rescue the cellular phenotypes induced by MECP2-overexpression in Drosophila. And biochemical assays using mice and cell culture systems show that MeCP2 and E6AP physically interact and regulate the expression of shared target genes. Together these data suggest that MeCP2 and E6AP play a role in the transcriptional control of common target gene expression and provide some insight into why RTT and AS share several neurological phenotypes.",
keywords = "Angelman syndrome, MeCP2, Rett syndrome, Ube3a/E6AP",
author = "Soeun Kim and Maria Chahrour and Shay Ben-Shachar and Janghoo Lim",
year = "2013",
month = "7",
day = "19",
doi = "10.1016/j.bbrc.2013.06.036",
language = "English (US)",
volume = "437",
pages = "67--73",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Ube3a/E6AP is involved in a subset of MeCP2 functions

AU - Kim, Soeun

AU - Chahrour, Maria

AU - Ben-Shachar, Shay

AU - Lim, Janghoo

PY - 2013/7/19

Y1 - 2013/7/19

N2 - Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that share many clinical features. The disease-causing mutations have been identified for both syndromes. Mutations in Methyl-CpG Binding Protein 2 (MECP2) are found in a majority of patients with classical RTT while absence of maternal allele or intragenic mutation in the maternal copy of UBE3A gene encoding the human papilloma virus E6-associated protein (E6AP) cause most cases of AS. Extensive studies have been performed to determine the cause of the neurological problems in each disease. However, the genetic and molecular basis of the overlap in phenotypes between RTT and AS remains largely unknown. Here we present evidence that the phenotypic similarities between the two syndromes might be due to the shared molecular functions between MeCP2 and E6AP in gene expression. Our genetic and biochemical studies suggest that E6AP acts as an essential cofactor for a subset of MeCP2 functions. Specifically, decreased expression of Ube3a was able to rescue the cellular phenotypes induced by MECP2-overexpression in Drosophila. And biochemical assays using mice and cell culture systems show that MeCP2 and E6AP physically interact and regulate the expression of shared target genes. Together these data suggest that MeCP2 and E6AP play a role in the transcriptional control of common target gene expression and provide some insight into why RTT and AS share several neurological phenotypes.

AB - Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological disorders that share many clinical features. The disease-causing mutations have been identified for both syndromes. Mutations in Methyl-CpG Binding Protein 2 (MECP2) are found in a majority of patients with classical RTT while absence of maternal allele or intragenic mutation in the maternal copy of UBE3A gene encoding the human papilloma virus E6-associated protein (E6AP) cause most cases of AS. Extensive studies have been performed to determine the cause of the neurological problems in each disease. However, the genetic and molecular basis of the overlap in phenotypes between RTT and AS remains largely unknown. Here we present evidence that the phenotypic similarities between the two syndromes might be due to the shared molecular functions between MeCP2 and E6AP in gene expression. Our genetic and biochemical studies suggest that E6AP acts as an essential cofactor for a subset of MeCP2 functions. Specifically, decreased expression of Ube3a was able to rescue the cellular phenotypes induced by MECP2-overexpression in Drosophila. And biochemical assays using mice and cell culture systems show that MeCP2 and E6AP physically interact and regulate the expression of shared target genes. Together these data suggest that MeCP2 and E6AP play a role in the transcriptional control of common target gene expression and provide some insight into why RTT and AS share several neurological phenotypes.

KW - Angelman syndrome

KW - MeCP2

KW - Rett syndrome

KW - Ube3a/E6AP

UR - http://www.scopus.com/inward/record.url?scp=84880514835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880514835&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2013.06.036

DO - 10.1016/j.bbrc.2013.06.036

M3 - Article

VL - 437

SP - 67

EP - 73

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -