Imperial College London
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ProfessorBorisLenhard

Faculty of Medicine, Institute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 7594 0911b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

6.12CLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Li:2018:10.1101/gr.231449.117,
author = {Li, C and Lenhard, B and Luscombe, NM},
doi = {10.1101/gr.231449.117},
journal = {Genome Research},
pages = {676--688},
title = {Integrated analysis sheds light on evolutionary trajectories of young transcription start sites in the human genome},
url = {http://dx.doi.org/10.1101/gr.231449.117},
volume = {28},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Understanding the molecular mechanisms and evolution of the gene regulatory system remains a major challenge in biology. Transcription start sites (TSSs) are especially interesting because they are central to initiating gene expression. Previous studies revealed widespread transcription initiation and fast turnover of TSSs in mammalian genomes. Yet, how new TSSs originate and how they evolve over time remain poorly understood. To address these questions, we analyzed ∼200,000 human TSSs by integrating evolutionary (inter- and intra-species) and functional genomic data, particularly focusing on evolutionarily young TSSs that emerged in the primate lineage. TSSs were grouped according to their evolutionary age using sequence alignment information as a proxy. Comparisons of young and old TSSs revealed that (1) new TSSs emerge through a combination of intrinsic factors, like the sequence properties of transposable elements and tandem repeats, and extrinsic factors such as their proximity to existing regulatory modules; (2) new TSSs undergo rapid evolution that reduces the inherent instability of repeat sequences associated with a high propensity of TSS emergence; and (3) once established, the transcriptional competence of surviving TSSs is gradually enhanced, with evolutionary changes subject to temporal (fewer regulatory changes in younger TSSs) and spatial constraints (fewer regulatory changes in more isolated TSSs). These findings advance our understanding of how regulatory innovations arise in the genome throughout evolution and highlight the genomic robustness and evolvability in these processes.
AU  - Li,C
AU  - Lenhard,B
AU  - Luscombe,NM
DO  - 10.1101/gr.231449.117
EP  - 688
PY  - 2018///
SN  - 1088-9051
SP  - 676
TI  - Integrated analysis sheds light on evolutionary trajectories of young transcription start sites in the human genome
T2  - Genome Research
UR  - http://dx.doi.org/10.1101/gr.231449.117
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29618487
UR  - http://hdl.handle.net/10044/1/59023
VL  - 28
ER  -
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