Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53.
The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not clear. We report that LTR class I endogenous retrovirus (ERV) retroelements impact considerably the transcriptional network of human tumor suppressor protein p53. A total of 1,509 of approximately 319,000 human ERV LTR regions have a near-perfect p53 DNA binding site. The LTR10 and MER61 families are particularly enriched for copies with a p53 site. These ERV families are primate-specific and transposed actively near the time when the New World and Old World monkey lineages split. Other mammalian species lack these p53 response elements. Analysis of published genomewide ChIP data for p53 indicates that more than one-third of identified p53 binding sites are accounted for by ERV copies with a p53 site. ChIP and expression studies for individual genes indicate that human ERV p53 sites are likely part of the p53 transcriptional program and direct regulation of p53 target genes. These results demonstrate how retroelements can significantly shape the regulatory network of a transcription factor in a species-specific manner.
Wang
Ting
T
Center for Biomolecular Science and Engineering, and Howard Hughes Medical Institute, University of California, Santa Cruz, CA 95064, USA.
Zeng
Jue
J
Lowe
Craig B
CB
Sellers
Robert G
RG
Salama
Sofie R
SR
Yang
Min
M
Burgess
Shawn M
SM
Brachmann
Rainer K
RK
Haussler
David
D
D001665:Binding Sites; D045744:Cell Line, Tumor; D020077:Endogenous Retroviruses / Q000145:classification / Q000502:physiology*; D019143:Evolution, Molecular; D018628:Gene Dosage / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D011485:Protein Binding; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53