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

  • Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization
We show that Primordial Germ Cells (PGCs) start zygotic genome activation with no delay and find no differences in transcriptional and chromatin opening compared to the somatic blastocysts. Unexpectedly, both PGC and somatic blastocysts activate germ-cell-specific genes, which are only stabilized in PGCs by cytoplasmic germ plasm determinants.However, perinuclear relocalization of germ plasm during PGC migration is coupled to dramatic divergence between PGC and somatic transcriptome and epigenomes and dependent on the germ factor Tdrd7.
https://doi.org/10.1016/j.devcel.2021.02.007

  • 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.