Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses

• DOI: 10.1371/journal.pgen.1006883
• Publication Date: 2017-07-13T16:11:58Z
• Authors: Jumpei Ito; Ryota Sugimoto; Hirofumi Nakaoka; Shiro Yamada; Tetsuaki Kimura; Takahide Hayano; Ituro Inoue
• Keywords: DNA binding site; Endogenous retrovirus; GATA transcription factor

Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified characterized these based on publicly available datasets ChIP-Seq 97 factors (TFs) provided by ENCODE Roadmap Epigenomics projects. determined factor-binding sites (TFBSs) using TFBSs observed HERV/LTR sequences (HERV-TFBSs). Overall, 794,972 HERV-TFBSs were identified. Subsequently, we "HERV/LTR-shared element (HSRE)," defined as a TF-binding motif in HERV-TFBSs, shared within substantial fraction type. HSREs could be an indication HERV/LTRs are present before their insertions. 2,201 HSREs, comprising specific associations 354 84 TFs. Clustering analysis showed can grouped according to TF binding patterns; groups bounded pluripotent TFs (e.g., SOX2, POU5F1, NANOG), embryonic endoderm/mesendoderm GATA4/6, SOX17, FOXA1/2), hematopoietic SPI1 (PU1), GATA1/2, TAL1), CTCF Regulatory tended locate nearby and/or interact three-dimensionally with genes involved immune responses, indicating play important role controlling network. Further, demonstrated subgroup-specific LTR7, LTR5B, LTR5_Hs, gains or losses occurred during genomic invasions HERV/LTRs. Finally, constructed dbHERV-REs, interactive database (http://herv-tfbs.com/). This study provides fundamental information understanding impact transcription, offers insights into transcriptional modulation systems ancestral HERVs.