Life Sciences Research for Lifelong Health

Simon Andrews

Simon Andrews did his first degree in Microbiology at the University of Warwick.  After a breif period working for Sandoz pharmaceuticals he went on  to do a PhD in protein engineering a the University of Newcastle with Harry Gilbert.  During his PhD his interests moved from bench work toward the emerging field of bioinformatics, and he decided to follow this direction in his future career.

After completing his PhD Simon worked with the BBSRC IT Services where he developed and then presented a series of bioinformatics training courses in protein structure analysis to the BBSRC institutes.  At one of these courses at Babraham he met John Coadwell who establised the Babraham bioinformatics group and was then employed as the second member of the bioinformatics team.  Since joining Babraham Simon has seen the group grow from two people to nine as the field has become far more prominent in the biological research community.  He took over the running of the group in 2010.

Latest Publications

MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.
Hanna CW, Taudt A, Huang J, Gahurova L, Kranz A, Andrews S, Dean W, Stewart AF, Colomé-Tatché M, Kelsey G

Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase gene Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had limited effects on transcription-coupled H3K4 trimethylation or gene expression. Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.

+ View Abstract

Nature structural & molecular biology, 25, 1545-9985, 73-82, 2018

PMID: 29323282

Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(D)J Recombination.
Matheson LS, Bolland DJ, Chovanec P, Krueger F, Andrews S, Koohy H, Corcoran AE

V(D)J recombination is essential for the generation of diverse antigen receptor (AgR) repertoires. In B cells, immunoglobulin kappa (Igκ) light chain recombination follows immunoglobulin heavy chain (Igh) recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS) of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh, as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(D)J recombination and provide avenues for further investigation of chromatin signatures that may underpin V(D)J-mediated chromosomal translocations.

+ View Abstract

Frontiers in immunology, 8, 1664-3224, 1550, 2017

PMID: 29204143

An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells.
Berrens RV, Andrews S, Spensberger D, Santos F, Dean W, Gould P, Sharif J, Olova N, Chandra T, Koseki H, von Meyenn F, Reik W

Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.

+ View Abstract

Cell stem cell, 21, 1875-9777, 694-703.e7, 2017

PMID: 29100015

01223 496463

Email Simon
View Profile



Facility Members

Latest Publications

MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.

Hanna CW, Taudt A, Huang J

Nature structural & molecular biology
25 1545-9985:73-82 (2018)

PMID: 29323282

An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells.

Berrens RV, Andrews S, Spensberger D

Cell stem cell
21 1875-9777:694-703.e7 (2017)

PMID: 29100015

Transcription and chromatin determinants of de novo DNA methylation timing in oocytes.

Gahurova L, Tomizawa SI, Smallwood SA

Epigenetics & chromatin
10 1756-8935:25 (2017)

PMID: 28507606