We are a computational group based in the MRC London Institute of Medical Sciences at Imperial College headed by Boris Lenhard. Our major research interests focus on:

  • Structure and function of gene promoters
  • Function and genomic distribution of gene regulatory elements
  • Function of transcription factors
  • Regulation of the production of transcription factors i.e. transcriptional regulatory networks (TRNs)
  • Association of different modes of regulation with epigenetic marks and their inheritance
  • Transcriptional and translational regulation and dynamics in embryonic development
  • The role of core promoters and their diverse architectures in vertebrate development and differentiation
  • Emergence and evolutionary dynamics of conserved non-coding elements

Most of our work until now has been purely computational, either analysing publicly available data or in collaboration with experimental laboratories using high-throughput sequencing techniques such as CAGE, ATAC-seq, MNase-seq, RNA-seq, ChIP-seq and Hi-C. Since 2016 we also have experimental activity focusing on studying functional diversity of promoters in development and differentiation.

 

Visual Abstracts

  • Global regulatory transitions at core promoters demarcate the mammalian germline cycle
Global regulatory transitions at core promoters demarcate the mammalian germline cycle
Canonical somatic +1 nucleosome-dependent, alternative +1 nucleosome dependent and maternal transcription initiation grammar.
Somatic canonical +1 nucleosome-dependent grammar is used in primordial germ cells, early gonadal germ cells and embryo upon zygotic genome activation. Alternative +1 nucleosome-dependent grammar is used in late gonadal germ cells. Maternal W-box grammar is used in oocytes. Two promoter architecture classes are shown – single W-box leading to a narrow transcription initiation, and multiple W-boxes leading to a broad transcription initiation pattern, distinct from the +1 nucleosome somatic type.
https://www.biorxiv.org/content/10.1101/2020.10.30.361865v1

  • Transcriptome-wide capping of mRNA fragments
We propose two cellular mechanisms presumed involved in the formation of recapped 3’UTR-associated RNAs (uaRNAs). The first one suggests that recapping happens through the degradation process which is triggered by non-sense mediated decay (NMD). Where the second one suggests that the cleavage site is formed by Ago2 binding to a stem-loop structure guided by miRNA or RNAi, or without guidance binding to G-rich motifs together with UPF1. Both mechanisms are currently undergoing experimental validation.