Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos.
Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos.
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DOI：
10.1038/srep28995
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发表时间：
2016-07-14
影响因子：
4.6
通讯作者：
Kere J
中科院分区：
文献类型：
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作者：
Madissoon E;Jouhilahti EM;Vesterlund L;Töhönen V;Krjutškov K;Petropoulos S;Einarsdottir E;Linnarsson S;Lanner F;Månsson R;Hovatta O;Bürglin TR;Katayama S;Kere J
PAIRED（PRD）样同源异型盒基因属于一类预测转录因子基因。这些PRD样同源框基因中的几个已经从基因组序列中通过计算机预测，但直到最近才有转录表达的证据。我们最近发现9个PRD样同源盒基因ARGFX、CPHX1、CPHX2、DPRX、DUXA、DUXB、NOBOX、TPRX1和TPRX2在人类植入前胚胎中表达。在本研究中，我们深入研究了这些PRD样同源盒基因的特征，并研究了它们作为转录因子的功能。我们从人类胚胎中克隆了多个转录变体，并表明这些基因的表达对胚胎和多能干细胞具有特异性。这些基因在人胚胎干细胞中的过表达证实了它们作为转录因子的作用，即激活因子（CPHX 1、CPHX 2、ARGFX）或阻遏因子（DPRX、DUXA、TPRX2），其具有不同的靶点，可以通过同源结构域中的氨基酸序列来解释。一些PRD样同源结构域转录因子具有高度一致性的靶基因，并显示富集发育重要的基因集和36 bp的DNA识别基序参与胚胎基因组激活（EGA）。我们的数据暗示了这些以前未表征的PRD样同源结构域蛋白在调节人类胚胎基因组激活和植入前胚胎发育中的作用。
PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.