MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

Rebekah Tillotson Research Group

Mechanistic understanding of chromatinopathies

Dr Rebekah Tillotson, Chancellor’s Fellow
Dr Rebekah Tillotson, Chancellor’s Fellow

Research in a Nutshell

Almost all cells in a multicellular organism contain the same instruction manual – their DNA. To develop different specialised cell types (e.g. neurons), the expression level of genes must be properly regulated. This is controlled by a family of proteins called chromatin factors. While complete loss of a single chromatin factor is often incompatible with mammalian life, mutations that partially disrupt their activity or alter dosage result in “chromatinopathies” – monogenetic disorders affecting multiple tissues, always including the brain. Individually, these disorders are rare (with a prevalence of <1 in 2,000 people), but collectively they affect millions of people worldwide. By investigating how biological processes are disrupted in chromatinopathies, we dissect how chromatin factors function and aim to uncover therapeutic strategies.

We are initially focusing on ATR-X syndrome, caused by hypomorphic mutations in the X-linked ATRX gene in males. ATRX is a chromatin remodelling ATPase, which has been implicated in DNA damage repair, heterochromatin maintenance and gene regulation. We use cellular and mouse models to determine the critical roles of ATRX, how molecular pathways are disrupted in ATR-X syndrome and whether features of this disease are treatable after birth, particularly a particulary focus on neurological function. We will subsequently expand our research to other “chromatinopathies” with the goal of identifying shared molecular mechanisms that can be targeted by common treatments.


Rebekah Tillotson Group Leader
Ruimin Zhao (Zoey) MScR Student



  1. Tillotson R, Yan K, Ruston J, DeYoung T, Córdova A, Turcotte-Cardin V, Yee Y, Taylor C, Visuvanathan S, Babbs C, et al. (2023). A new mouse model of ATR-X syndrome carrying a common patient mutation exhibits neurological and morphological defects. Hum Mol Genet. 32:2485-2501 DOI: 10.1093/hmg/ddad075.
  2. Tillotson R, Cholewa-Waclaw J, Chhatbar K, Connelly J, Kirschner SA, Webb S, Koerner MV, Selfridge J, Kelly D, de Sousa D, et al. (2021). Neuronal non-CG methylation is an essential target for MeCP2 function. Mol Cell 81:1260–1275. DOI: 10.1101/2020.07.02.184614.
  3. Tillotson R, Selfridge J, Koerner MV, Gadalla KKE, Guy J, De Sousa D, Hector RD, Cobb SR, Bird A. (2017). Radically truncated MeCP2 rescues Rett syndrome-like neurological defects. Nature 550: 398–401. DOI: 10.1038/nature24058.
  4. Tillotson R, Bird A. (2019). The Molecular Basis of MeCP2 Function in the Brain. J Mol Biol 432: 1602–1623. DOI 10.1016/j.jmb.2019.10.004.


  • Professor Yanick Crow, The University of Edinburgh 
  • Dr Tom Deegan, The University of Edinburgh
  • Professor David Picketts, Ottawa Hospital Research Institute, Canada

Partners and Funders

  • Chancellor’s Fellowship (2024-2029)


Scientific Themes

chromatin, intellectual disability, disease mechanisms, rare disease

Technology Expertise

Genome editing, Mammalian Cell Culture, Mouse Neurobehavioural Phenotyping, Biochemistry, Molecular Biology