Abstract
Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.
| Original language | English |
|---|---|
| Pages (from-to) | 485-490 |
| Number of pages | 6 |
| Journal | Genes and Development |
| Volume | 27 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2013 Mar 1 |
| Externally published | Yes |
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Keywords
- 3' UTR
- HDAC4
- Human fetal brain
- MeCP2
- miR-483-5p
- TBL1X
ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. / Han, Kihoon; Gennarino, Vincenzo Alessandro; Lee, Yoontae; Pang, Kaifang; Hashimoto-Torii, Kazue; Choufani, Sanaa; Raju, Chandrasekhar S.; Oldham, Michael C.; Weksberg, Rosanna; Rakic, Pasko; Liu, Zhandong; Zoghbi, Huda Y.
In: Genes and Development, Vol. 27, No. 5, 01.03.2013, p. 485-490.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p
AU - Han, Kihoon
AU - Gennarino, Vincenzo Alessandro
AU - Lee, Yoontae
AU - Pang, Kaifang
AU - Hashimoto-Torii, Kazue
AU - Choufani, Sanaa
AU - Raju, Chandrasekhar S.
AU - Oldham, Michael C.
AU - Weksberg, Rosanna
AU - Rakic, Pasko
AU - Liu, Zhandong
AU - Zoghbi, Huda Y.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.
AB - Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.
KW - 3' UTR
KW - HDAC4
KW - Human fetal brain
KW - MeCP2
KW - miR-483-5p
KW - TBL1X
UR - http://www.scopus.com/inward/record.url?scp=84874895206&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874895206&partnerID=8YFLogxK
U2 - 10.1101/gad.207456.112
DO - 10.1101/gad.207456.112
M3 - Article
C2 - 23431031
AN - SCOPUS:84874895206
VL - 27
SP - 485
EP - 490
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 5
ER -