Imperial College London

ProfessorBorisLenhard

Faculty of MedicineInstitute of Clinical Sciences

Professor of Computational Biology
 
 
 
//

Contact

 

+44 (0)20 3313 8353b.lenhard Website

 
 
//

Assistant

 

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

 
//

Location

 

230ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Wragg:2020:nar/gkaa563,
author = {Wragg, JW and Roos, L and Vucenovic, D and Cvetesic, N and Lenhard, B and Müller, F},
doi = {nar/gkaa563},
journal = {Nucleic Acids Res},
title = {Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation.},
url = {http://dx.doi.org/10.1093/nar/gkaa563},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The core-promoter, a stretch of DNA surrounding the transcription start site (TSS), is a major integration-point for regulatory-signals controlling gene-transcription. Cellular differentiation is marked by divergence in transcriptional repertoire and cell-cycling behaviour between cells of different fates. The role promoter-associated gene-regulatory-networks play in development-associated transitions in cell-cycle-dynamics is poorly understood. This study demonstrates in a vertebrate embryo, how core-promoter variations define transcriptional output in cells transitioning from a proliferative to cell-lineage specifying phenotype. Assessment of cell proliferation across zebrafish embryo segmentation, using the FUCCI transgenic cell-cycle-phase marker, revealed a spatial and lineage-specific separation in cell-cycling behaviour. To investigate the role differential promoter usage plays in this process, cap-analysis-of-gene-expression (CAGE) was performed on cells segregated by cycling dynamics. This analysis revealed a dramatic increase in tissue-specific gene expression, concurrent with slowed cycling behaviour. We revealed a distinct sharpening in TSS utilization in genes upregulated in slowly cycling, differentiating tissues, associated with enhanced utilization of the TATA-box, in addition to Sp1 binding-sites. In contrast, genes upregulated in rapidly cycling cells carry broad distribution of TSS utilization, coupled with enrichment for the CCAAT-box. These promoter features appear to correspond to cell-cycle-dynamic rather than tissue/cell-lineage origin. Moreover, we observed genes with cell-cycle-dynamic-associated transitioning in TSS distribution and differential utilization of alternative promoters. These results demonstrate the regulatory role of core-promoters in cell-cycle-dependent transcription regulation, during embryo-development.
AU - Wragg,JW
AU - Roos,L
AU - Vucenovic,D
AU - Cvetesic,N
AU - Lenhard,B
AU - Müller,F
DO - nar/gkaa563
PY - 2020///
TI - Embryonic tissue differentiation is characterized by transitions in cell cycle dynamic-associated core promoter regulation.
T2 - Nucleic Acids Res
UR - http://dx.doi.org/10.1093/nar/gkaa563
UR - https://www.ncbi.nlm.nih.gov/pubmed/32619237
ER -