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Cavβ1a 亚基调节基因表达并抑制肌肉祖细胞中的肌生成素。

The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.

机构信息

Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157.

Department of Internal Medicine-Gerontology, Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157 Biochemistry Research Institute of La Plata (INIBIOLP)/National Scientific and Technical Research Council (CONICET), School of Medicine, National University of La Plata, 1900 La Plata, BA, Argentina.

出版信息

J Cell Biol. 2014 Jun 23;205(6):829-46. doi: 10.1083/jcb.201403021. Epub 2014 Jun 16.

DOI:10.1083/jcb.201403021
PMID:24934157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4068134/
Abstract

Voltage-gated calcium channel (Cav) β subunits are auxiliary subunits to Cavs. Recent reports show Cavβ subunits may enter the nucleus and suggest a role in transcriptional regulation, but the physiological relevance of this localization remains unclear. We sought to define the nuclear function of Cavβ in muscle progenitor cells (MPCs). We found that Cavβ1a is expressed in proliferating MPCs, before expression of the calcium conducting subunit Cav1.1, and enters the nucleus. Loss of Cavβ1a expression impaired MPC expansion in vitro and in vivo and caused widespread changes in global gene expression, including up-regulation of myogenin. Additionally, we found that Cavβ1a localizes to the promoter region of a number of genes, preferentially at noncanonical (NC) E-box sites. Cavβ1a binds to a region of the Myog promoter containing an NC E-box, suggesting a mechanism for inhibition of myogenin gene expression. This work indicates that Cavβ1a acts as a Cav-independent regulator of gene expression in MPCs, and is required for their normal expansion during myogenic development.

摘要

电压门控钙通道（Cav）β亚基是 Cav 的辅助亚基。最近的报告表明，Cavβ亚基可能进入细胞核，并暗示在转录调控中发挥作用，但这种定位的生理相关性尚不清楚。我们试图确定 Cavβ在肌肉祖细胞（MPCs）中的核功能。我们发现，Cavβ1a 在增殖的 MPC 中表达，在钙传导亚基 Cav1.1 表达之前，并进入细胞核。Cavβ1a 表达的缺失会损害体外和体内 MPC 的扩增，并导致全局基因表达的广泛变化，包括肌生成素的上调。此外，我们发现 Cavβ1a 定位于许多基因的启动子区域，优先定位于非典型（NC）E 盒位点。Cavβ1a 与含有 NC E 盒的 Myog 启动子区域结合，表明抑制肌生成素基因表达的一种机制。这项工作表明，Cavβ1a 作为 Cav 非依赖性的 MPC 基因表达调节剂发挥作用，并且是其在肌生成发育过程中正常扩增所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/a33a9f947104/JCB_201403021_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/82b5cff0fb58/JCB_201403021_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/ac6675bbe933/JCB_201403021_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/a2aae7373448/JCB_201403021_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/ad480d59effe/JCB_201403021_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/aca66e50ac4e/JCB_201403021_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/4b0de6ade3b0/JCB_201403021_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/ba328d3292c7/JCB_201403021_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/b89179f4c43b/JCB_201403021_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/45bde93b59c4/JCB_201403021_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/a33a9f947104/JCB_201403021_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/82b5cff0fb58/JCB_201403021_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/ac6675bbe933/JCB_201403021_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/a2aae7373448/JCB_201403021_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/ad480d59effe/JCB_201403021_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/aca66e50ac4e/JCB_201403021_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/4b0de6ade3b0/JCB_201403021_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/ba328d3292c7/JCB_201403021_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/b89179f4c43b/JCB_201403021_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/45bde93b59c4/JCB_201403021_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8864/4068134/a33a9f947104/JCB_201403021_Fig10.jpg

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