Imperial College London

ProfessorBorisLenhard

Faculty of MedicineInstitute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

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

 
 
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Assistant

 

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

 
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Location

 

230ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cantone:2017:10.1186/s13059-016-1136-4,
author = {Cantone, I and Dharmalingam, G and Chan, YW and Kohler, AC and Lenhard, B and Merkenschlager, M and Fisher, AG},
doi = {10.1186/s13059-016-1136-4},
journal = {Genome Biology},
title = {Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation},
url = {http://dx.doi.org/10.1186/s13059-016-1136-4},
volume = {18},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BackgroundInactivation of one X chromosome is established early in female mammalian development and can be reversed in vivo and in vitro when pluripotency factors are re-expressed. The extent of reactivation along the inactive X chromosome (Xi) and the determinants of locus susceptibility are, however, poorly understood. Here we use cell fusion-mediated pluripotent reprograming to study human Xi reactivation and allele-specific single nucleotide polymorphisms (SNPs) to identify reactivated loci.ResultsWe show that a subset of human Xi genes is rapidly reactivated upon re-expression of the pluripotency network. These genes lie within the most evolutionary recent segments of the human X chromosome that are depleted of LINE1 and enriched for SINE elements, predicted to impair XIST spreading. Interestingly, this cadre of genes displays stochastic Xi expression in human fibroblasts ahead of reprograming. This stochastic variability is evident between clones, by RNA-sequencing, and at the single-cell level, by RNA-FISH, and is not attributable to differences in repressive histone H3K9me3 or H3K27me3 levels. Treatment with the DNA demethylating agent 5-deoxy-azacytidine does not increase Xi expression ahead of reprograming, but instead reveals a second cadre of genes that only become susceptible to reactivation upon induction of pluripotency.ConclusionsCollectively, these data not only underscore the multiple pathways that contribute to maintaining silencing along the human Xi chromosome but also suggest that transcriptional stochasticity among human cells could be useful for predicting and engineering epigenetic strategies to achieve locus-specific or domain-specific human Xi gene reactivation.
AU - Cantone,I
AU - Dharmalingam,G
AU - Chan,YW
AU - Kohler,AC
AU - Lenhard,B
AU - Merkenschlager,M
AU - Fisher,AG
DO - 10.1186/s13059-016-1136-4
PY - 2017///
SN - 1474-760X
TI - Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation
T2 - Genome Biology
UR - http://dx.doi.org/10.1186/s13059-016-1136-4
UR - http://hdl.handle.net/10044/1/43971
VL - 18
ER -