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鉴定和描述影响表达和神经功能的保守非编码调控元件。

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

机构信息

Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.

Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

出版信息

Genes Dev. 2021 Apr 1;35(7-8):489-494. doi: 10.1101/gad.345397.120. Epub 2021 Mar 18.

DOI:10.1101/gad.345397.120
PMID:33737384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8015713/
Abstract

While changes in MeCP2 dosage cause Rett syndrome (RTT) and duplication syndrome (MDS), its transcriptional regulation is poorly understood. Here, we identified six putative noncoding regulatory elements of , 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 and highlights genomic sites that could serve as diagnostic and therapeutic targets in RTT or MDS.

摘要

虽然 MeCP2 剂量的变化会导致雷特综合征（RTT）和 重复综合征（MDS），但其转录调控却知之甚少。在这里，我们鉴定了 的六个可能的非编码调节元件，其中两个在人类中保守。在小鼠和人类 iPSC 衍生神经元中缺失后，这些元件以相反的方向改变了 RNA 和蛋白质水平，并导致小鼠出现部分 RTT 和 MDS 样行为缺陷。我们的发现为 的转录调控提供了深入了解，并突出了可能作为 RTT 或 MDS 诊断和治疗靶点的基因组位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/725c8f920218/489f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/f922122ad65c/489f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/90393c5ebc9b/489f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/6798e02ed701/489f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/1e8dc4cb80b6/489f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/725c8f920218/489f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/f922122ad65c/489f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/90393c5ebc9b/489f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/6798e02ed701/489f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/1e8dc4cb80b6/489f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8e/8015713/725c8f920218/489f05.jpg

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