Genomic and epigenomic regulation of cell fate

Multicellular organisms are composed of hundreds of cells types with an identical genome. DNA is packaged in the form of “chromatin” including nucleosomes, epigenetic modifications and a large number of proteins associated with transcription, remodelling or DNA repair. In this way, genetic information is decoded differently in each cell type, leading to distinct phenotypes and specialised functions.

How is cellular identity regulated during developmental processes, or disrupted in pathological conditions? Many molecular players are known to influence cell fate decisions, such as transcription factors and epigenetic regulators. However, how these macromolecules act together on chromatin to modulate gene expression programs remains poorly understood.

In our laboratory, we exploit a combination of cutting-edge genetic engineering, biochemical assays and high-throughput sequencing technologies to dissect the molecular mechanisms of proteins associated with chromatin. These factors are critical for embryonic development and often de-regulated in human diseases such as cancer and neurodevelopmental disorders.

We take advantage of embryonic stem cells as a model system for cell fate decisions. Using genetically manipulated pluripotent cells, we can assess not only the influence of proteins of interest on the transcriptome and epigenome, but also test their phenotypic impact on cellular differentiation in vitro.

RECENT PUBLICATIONS

MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation
Raphaël Pantier, Megan Brown, Sicheng Han , Katie Paton, Stephen Meek, Thomas Montavon, Nicholas Shukeir, Toni Mchugh, David Kelly, Tino Hochepied, Claude Libert, Thomas Jenuwein, Tom Burdon, Adrian Bird.
Nature Communications, 2024, 15 (1), pp.3880.
DOI: 10.1038/s41467-024-47395-1

Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome
James Watson, Raphaël Pantier, Uma Jayachandran, Kashyap Chhatbar, Beatrice Alexander-Howden, Valdeko Kruusvee, Michal Prendecki, Adrian Bird, Atlanta Cook.
Life Science Alliance, 2023, 6 (3), pp.e202201588.
DOI: 10.26508/lsa.202201588

High-throughput sequencing SELEX for the determination of DNA-binding protein specificities in vitro
Raphaël Pantier, Kashyap Chhatbar, Grace Alston , Heng Yang Lee, Adrian Bird. 
STAR Protoc. 2022 Sep 16;3(3):101490
DOI: 10.1016/j.xpro.2022.101490

SALL4 controls cell fate in response to DNA base composition
Raphaël Pantier, Kashyap Chhatbar, Timo Quante, Konstantina Skourti-Stathaki, Justyna Cholewa-Waclaw, Grace Alston, Beatrice Alexander-Howden, Heng Yang Lee, Atlanta Cook, Cornelia Spruijt, Michiel Vermeulen, Jim Selfridge, Adrian Bird.
Molecular Cell, 2021, 81 (4), pp.845-858.e8.
DOI: 10.1016/j.molcel.2020.11.046

TET1 Interacts Directly with NANOG via Independent Domains Containing Hydrophobic and Aromatic Residues
Raphaël Pantier, Nicholas Mullin, Elisa Hall-Ponsele, Ian Chambers.
Journal of Molecular Biology, 2020, 432 (23), pp.6075-6091.
DOI: 10.1016/j.jmb.2020.10.008

Endogenous epitope-tagging of Tet1, Tet2 and Tet3 identifies TET2 as a naïve pluripotency marker
Raphaël Pantier, Tülin Tatar, Douglas Colby, Ian Chambers.
Life Science Alliance, 2019, 2 (5), pp.e201900516.
DOI : 10.26508/lsa.201900516

A new twist to Sin3 complexes in pluripotent cells
Raphaël Pantier, Nicholas Mullin, Ian Chambers.
EMBO Journal, 2017, 36 (15), pp.2184-2186.
DOI : 10.15252/embj.201797516