Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types
Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types
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增强子转录识别感光细胞类型的顺式调控元件
DOI：
10.1101/513598
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Ivan P. Moskowitz
中科院分区：
文献类型：
--
作者：
Rangarajan D. Nadadur;Carlos Perez;Nicolas Lonfat;Linsin A. Smith;Andrew E. O. Hughes;Sui Wang;J. Corbo;Constance L Cepko;Ivan P. Moskowitz
鉴定在特定细胞类型中调控基因表达的顺式调控元件（克雷斯）对于定义控制正常生理和疾病状态的基因调控网络（GRNs）至关重要。我们先前利用非编码RNA（ncRNA）分析来定义在成年小鼠心脏中包含GRN的克雷斯1。在这里，我们应用ncRNA分析的存在和不存在的Nrl，视杆与视锥光感受器细胞的命运所需的视杆光感受器特异性转录因子的小鼠视网膜。Nrl依赖性ncRNA的差异表达与Nrl依赖性局部基因的差异表达呈正相关。平行地发现了两种不同的Nrl依赖性调节网络：Nrl激活的ncRNA在视杆细胞中富集了可接近的染色质，但在视锥细胞中却没有，而Nrl抑制的ncRNA在视锥细胞中富集了可接近的染色质，但在视杆细胞中却没有。此外，差异Nrl依赖性ncRNA表达水平与感光细胞类型特异性ATAC-seq读取密度定量相关。Nrl依赖性ncRNA定义的基因座的直接评估鉴定了功能性视锥光感受器克雷斯。这项工作支持差异ncRNA分析作为一个平台，用于识别上下文特异性调控元件，并提供了深入了解定义感光细胞类型的网络。
Identification of the cis-regulatory elements (CREs) that regulate gene expression in specific cell types is critical for defining the gene regulatory networks (GRNs) that control normal physiology and disease states. We previously utilized non-coding RNA (ncRNA) profiling to define CREs that comprise a GRN in the adult mouse heart1. Here, we applied ncRNA profiling to the mouse retina in the presence and absence of Nrl, a rod photoreceptor-specific transcription factor required for rod versus cone photoreceptor cell fate. Differential expression of Nrl-dependent ncRNAs positively correlated with differential expression of Nrl-dependent local genes. Two distinct Nrl-dependent regulatory networks were discerned in parallel: Nrl-activated ncRNAs were enriched for accessible chromatin in rods but not cones whereas Nrl-repressed ncRNAs were enriched for accessible chromatin in cones but not rods. Furthermore, differential Nrl-dependent ncRNA expression levels quantitatively correlated with photoreceptor cell type-specific ATAC-seq read density. Direct assessment of Nrl-dependent ncRNA-defined loci identified functional cone photoreceptor CREs. This work supports differential ncRNA profiling as a platform for identifying context-specific regulatory elements and provides insight into the networks that define photoreceptor cell types.
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DOI：
10.1073/pnas.0508214103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Akimoto, M;Cheng, H;Swaroop, A
通讯作者：
Swaroop, A
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
11.8
作者：
Emerson, Mark M.;Surzenko, Natalia;Goetz, Jillian J.;Trimarchi, Jeffrey;Cepko, Constance L.
通讯作者：
Cepko, Constance L.
影响因子：
8.8
作者：
Werner MS;Ruthenburg AJ
通讯作者：
Ruthenburg AJ
视锥细胞分化的胚胎标记。
影响因子：
2.2
作者：
Rodgers,HelenM;Belcastro,Marycharmain;Sokolov,Maxim;Mathers,PeterH
通讯作者：
Mathers,PeterH