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PARP-14 通过结合特定的 DNA 序列来促进 Th2 细胞基因表达。

PARP-14 binds specific DNA sequences to promote Th2 cell gene expression.

机构信息

Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

Department of Pediatrics, HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; School of Informatics, Indiana University-Purdue University, Indianapolis, Indianapolis, Indiana, United States of America.

出版信息

PLoS One. 2013 Dec 20;8(12):e83127. doi: 10.1371/journal.pone.0083127. eCollection 2013.

DOI:10.1371/journal.pone.0083127
PMID:24376650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3869773/
Abstract

PARP-14, a member of the poly ADP-ribose polymerase super family, promotes T helper cell 2 (Th2) differentiation by regulating interleukin-4 (IL-4) and STAT6-dependent transcription. Yet, whether PARP-14 globally impacts gene regulation has not been determined. In this report, using an RNA pol II ChIP-seq approach, we identify genes in Th2 cells that are regulated by PARP-14, and either dependent or independent of ADP-ribosyltransferase catalytic activity. Our data demonstrate that PARP-14 enhances the expression of Th2 genes as it represses the expression of Th1-associated genes. Among the relevant targets are Signal Transducer and Activator of Transcription genes required for polarizing Th1 and Th2 cells. To define a mechanism for PARP-14 function, we use an informatics approach to identify putative PARP-14 DNA binding sites. Two putative PARP-14 binding motifs are identified in multiple Th2 cytokine genes, and we demonstrate that PARP-14 interacts with each motif using in vitro binding assays. Taken together our results indicate that PARP-14 is an important factor for T helper cell differentiation and it binds to specific DNA sequences to mediate its function.

摘要

PARP-14 是聚 ADP-核糖聚合酶超家族的成员，通过调节白细胞介素-4（IL-4）和 STAT6 依赖性转录来促进辅助性 T 细胞 2（Th2）分化。然而，PARP-14 是否会全局影响基因调控尚未确定。在本报告中，我们使用 RNA pol II ChIP-seq 方法，鉴定了 Th2 细胞中受 PARP-14 调控的基因，这些基因依赖或不依赖 ADP-核糖基转移酶催化活性。我们的数据表明，PARP-14 通过抑制 Th1 相关基因的表达来增强 Th2 基因的表达。相关的靶基因包括极化 Th1 和 Th2 细胞所需的信号转导和转录激活因子基因。为了定义 PARP-14 功能的机制，我们使用信息学方法来识别可能的 PARP-14 DNA 结合位点。在多个 Th2 细胞因子基因中鉴定出两个可能的 PARP-14 结合基序，并且我们使用体外结合测定证明了 PARP-14 与每个基序相互作用。总之，我们的结果表明 PARP-14 是辅助性 T 细胞分化的重要因素，它结合到特定的 DNA 序列中来介导其功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/30a2c39fd805/pone.0083127.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/7e400e40a61e/pone.0083127.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/1f5ed2c41084/pone.0083127.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/2a77f0646e10/pone.0083127.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/aa7ade8b4f20/pone.0083127.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/30a2c39fd805/pone.0083127.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/7e400e40a61e/pone.0083127.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/1f5ed2c41084/pone.0083127.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/2a77f0646e10/pone.0083127.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/aa7ade8b4f20/pone.0083127.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/3869773/30a2c39fd805/pone.0083127.g005.jpg

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