Transposable elements (TEs) are major components of the human genome constituting at least half of it. More than half a century ago, Barbara McClintock and later Roy Britten and Eric Davidson have postulated that they might be major players in the host gene regulation. We have scanned a large amount of data produced by ENCODE project for active transcription binding sites (TFBSs) located in TE-originated parts of polymerase II promoters. In total, more than 35,000 promoters in six different tissues were analyzed and over 26,000 of them harbored TEs. Moreover, these TEs usually provide one or more of TFBSs in the host promoters, which resulted in more than 6% of active TFBSs in these regions located in the TE-originated sequences. Rewiring of transcription circuits played a major role in mammalian evolution and consequently increased their functional and morphological diversity. In this large-scale analysis, we have demonstrated that TEs contributed a large fraction of human TFBSs. Interestingly, these TFBSs usually act in a tissue-specific manner. Thus, our study clearly showed that TEs played a significant role in shaping expression pattern in mammals and humans in particular. Furthermore, since several TE families are still active in our genome, they continue to influence not only our genome architecture but also gene functioning in a broader sense.
This work was funded by the Institute of Bioinformatics, Muenster, Germany. We acknowledge support by Open Access Publication Fund of University of Muenster.
The author(s) declare that they have no conflict of interest.
SUPPORTING INFORMATION The supporting information is available online at
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Figure 1
Distribution of major types of TEs in the human genome. The promoter regions are depicted in the inner circle, while TE distribution in the rest of the human genome is presented in the outer circle.
Figure 2
Distribution of TE-derived sequences in the pol II promoter regions.
Figure 3
Fraction of promoter area occupied by TE-originated sequences. The promoters were analyzed using sliding window approach with wind size of
Figure 4
Distribution of TFBSs in different TE-families localized within promoter regions.
Figure 5
Pair-wise comparison of TFBSs’ uniqueness. Fraction of the query (
Tissue group | Number of TFs |
Blood | 360 |
Liver | 212 |
Kidney | 204 |
Breast | 93 |
Stem cells | 50 |
Lung | 50 |
Reproductive organs | 24 |
Bone marrow | 18 |
Fibroplast | 15 |
Nerve cells | 11 |
Digestive tract | 10 |
Prostatet gland | 6 |
Blood transport | 5 |
Muscle | 5 |
Pancreas | 5 |
Skin | 4 |
Lymph nodes or similar | 3 |
Spleen | 3 |
Parathyroid | 2 |
Adrenal gland | 2 |
Fat | 2 |
Retina | 1 |
TE family | Genome | Promoter regions | Non-promoter regions | |||||
Number of elements | Number of nucleotides | Number of elements | Number of nucleotides | Number of elements | Number of nucleotides | |||
LINE | 1,516,226 | 641,953,033 | 16,210 | 3,211,688 | 1,500,016 | 638,741,345 | ||
SINE | 1,779,271 | 392,908,499 | 32,368 | 6,655,074 | 1,746,903 | 386,253,425 | ||
LTR | 725,763 | 268,434,413 | 6,549 | 1,719,349 | 719,214 | 266,715,064 | ||
DNA | 489,391 | 103,055,478 | 6,487 | 1,042,442 | 482,904 | 102,013,036 | ||
Retroposon | 5,397 | 4,223,296 | 50 | 7,089 | 5,347 | 4,216,207 | ||
Unknown | 5,531 | 737,222 | 55 | 6,043 | 5,476 | 731,179 | ||
Total | 4,521,579 | 1,411,311,941 | 61,719 | 12,641,685 | 4,459,860 | 1,398,670,256 | ||
Gene ID | Gene name | Fraction of TE-derived sequences | TE elements | Gene type |
ENSG00000154415.7 | 0.95 | LTR | Protein coding | |
ENSG00000166228.8 | 0.92 | LINE | Protein coding | |
ENSG00000233480.1 | 0.94 | LINE | LincRNA | |
ENSG00000257729.2 | 0.95 | Different types | LincRNA | |
ENSG00000258969.1 | 0.93 | LTR | LincRNA | |
ENSG00000267543.1 | 1.00 | Different types | Sense intronic | |
ENSG00000272386.1 | 1.00 | Different types | Sense intronic | |
ENSG00000285191.1 | 0.95 | Different types | LincRNA |
Tissue | Pathway name | KEGG number |
Blood | Aminoacyl-tRNA biosynthesis | hsa00970 |
Basal transcription factors | hsa03022 | |
Citrate cycle (TCA cycle) | hsa00020 | |
DNA replication | hsa03030 | |
NF-κB signaling pathway | hsa04064 | |
Nucleotide excision repair | hsa03420 | |
Oxidative phosphorylation | hsa00190 | |
Proteasome | hsa03050 | |
Protein export | hsa03060 | |
Ribosome | hsa03010 | |
RNA transport | hsa03013 | |
SNARE interactions in vesicular transport | hsa04130 | |
Ubiquinone and other terpenoid-quinone biosynthesis | hsa00130 | |
Breast | Metabolic pathways | hsa01100 |
Non-alcoholic fatty liver disease (NAFLD) | hsa04932 | |
Oxidative phosphorylation | hsa00190 | |
Kidney | Nucleotide excision repair | hsa00190 |
Non-alcoholic fatty liver disease (NAFLD) | hsa04932 | |
Oxidative phosphorylation | hsa00190 | |
Liver | Bacterial invasion of epithelial cells | hsa05100 |
Carbon metabolism | hsa01200 | |
Citrate cycle (TCA cycle) | hsa00020 | |
Non-alcoholic fatty liver disease (NAFLD) | hsa04932 | |
Ribosome | hsa05120 | |
Lung | Epithelial cell signaling in Helicobacter pylori infection | hsa03010 |
Ribosome | hsa05120 | |
Stem cells | No enrichment | |
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