Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions

While changes in MeCP2 dosage cause Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of Mecp2, two of which are conserved in humans. Upon deletion in mice and human iPSC-deriv...

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Autores principales: Shao, Yingyao, Bajikar, Sameer S., Tirumala, Harini P., Gutierrez, Manuel Cantu, Wythe, Joshua D., Zoghbi, Huda Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2021
Materias:
Research Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015713/
https://www.ncbi.nlm.nih.gov/pubmed/33737384
http://dx.doi.org/10.1101/gad.345397.120
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author Shao, Yingyao
Bajikar, Sameer S.
Tirumala, Harini P.
Gutierrez, Manuel Cantu
Wythe, Joshua D.
Zoghbi, Huda Y.
author_facet Shao, Yingyao
Bajikar, Sameer S.
Tirumala, Harini P.
Gutierrez, Manuel Cantu
Wythe, Joshua D.
Zoghbi, Huda Y.
author_sort Shao, Yingyao
collection PubMed
description While changes in MeCP2 dosage cause Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of Mecp2, two of which are conserved in humans. Upon deletion in mice and human iPSC-derived neurons, these elements altered RNA and protein levels in opposite directions and resulted in a subset of RTT- and MDS-like behavioral deficits in mice. Our discovery provides insight into transcriptional regulation of Mecp2/MECP2 and highlights genomic sites that could serve as diagnostic and therapeutic targets in RTT or MDS.
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spelling pubmed-80157132021-10-01 Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions Shao, Yingyao Bajikar, Sameer S. Tirumala, Harini P. Gutierrez, Manuel Cantu Wythe, Joshua D. Zoghbi, Huda Y. Genes Dev Research Communication While changes in MeCP2 dosage cause Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of Mecp2, two of which are conserved in humans. Upon deletion in mice and human iPSC-derived neurons, these elements altered RNA and protein levels in opposite directions and resulted in a subset of RTT- and MDS-like behavioral deficits in mice. Our discovery provides insight into transcriptional regulation of Mecp2/MECP2 and highlights genomic sites that could serve as diagnostic and therapeutic targets in RTT or MDS. Cold Spring Harbor Laboratory Press 2021-04-01 /pmc/articles/PMC8015713/ /pubmed/33737384 http://dx.doi.org/10.1101/gad.345397.120 Text en © 2021 Shao et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Communication
Shao, Yingyao
Bajikar, Sameer S.
Tirumala, Harini P.
Gutierrez, Manuel Cantu
Wythe, Joshua D.
Zoghbi, Huda Y.
Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
title Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
title_full Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
title_fullStr Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
title_full_unstemmed Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
title_short Identification and characterization of conserved noncoding cis-regulatory elements that impact Mecp2 expression and neurological functions
title_sort identification and characterization of conserved noncoding cis-regulatory elements that impact mecp2 expression and neurological functions
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015713/
https://www.ncbi.nlm.nih.gov/pubmed/33737384
http://dx.doi.org/10.1101/gad.345397.120
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