Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Characterisation of ATRX, a chromatin remodelling protein

Funder MRC (part of UKRI)
Recipient organisation
Funding £1.4M
Period Mar 2017 — Mar 2022

In plain English

AI plain-English summary

Every cell in the human body carries the same DNA, yet a red blood cell churns out haemoglobin while a nerve cell never does—and a faulty protein that controls this switching process leaves children with severe learning difficulties, distinctive facial features, abnormal genital development, and anaemia. This condition, ATR-X syndrome, arises from mutations in a protein called ATRX, which helps package and unpack DNA to regulate which genes are active. Despite the revolution in human genome sequencing, scientists still do not understand how this packaging machinery works in detail. The project aims to determine exactly what ATRX does inside the cell and how its disruption leads to such a wide range of symptoms—likely because it perturbs the expression of many different genes. This is fundamental science. There is no immediate practical application. But understanding how a single protein can orchestrate the expression of multiple genes across different tissues could eventually point toward ways to mitigate the effects of ATR-X syndrome or other disorders where gene regulation goes awry. Similar fundamental work on chromatin remodelling has already reshaped how researchers think about cancer, development, and inherited disease.

View original technical description
Despite the revolution in genetics in the last decade and in particular the sequencing of the human genome, the regulation of gene expression largely remains a mystery. Every cell of the body contains a full complement of genes but only expresses a small repertoire required for that tissues function, such as the oxygen carrying protein, haemoglobin, in red blood cells. A complex hierarchy of regulation is emerging involving tissue-specific signals, chemical modifications to the DNA molecule and the proteins about which DNA is wrapped, enzymes that package and unpackage DNA and different cellular compartments that either favour or repress gene expression. Human genetic diseases are now being identified in which the components of this complex apparatus are disrupted. In one such condition, ATR-X syndrome, the affected children have profound learning difficulties, a characteristic facial appearance, abnormalities of genital development and a form of anaemia. It arises because of mutations in a protein involved in the regulation of gene expression. The diverse problems probably reflect the many different genes whose expression is perturbed. The overall aim of this programme is to determine the role of such proteins in the regulation of gene expression and their involvement in human disease.

View the original record at the funder ↗

Researchers

Richard Gibbons (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Structural and Functional Studies of ATRX- Syndrome Protein
Structural studies of the ATRX-DAXX chromatin remodeller complex and its role in heterochromatin and telomere maintenance
Using mechanistic understanding to develop treatments for ATR-X syndrome
Understanding the Role of Histone Variants in Tumorigenesis.
Understanding how Trithorax & Polycomb group proteins control gene expression from CpG islands

Original classification

Intramural

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.