Article Text

Download PDFPDF
Histones: coming of age in Mendelian genetic disorders

Abstract

Histones hold significant interest in development and genetic disorders due to their critical roles in chromatin dynamics, influencing gene expression and genome integrity. These roles are linked to alterations of post-translational marks, which are generally concentrated in the histone tails. The machinery modifying or interpreting these marks, known as chromatin writers, erasers or readers, have been associated with many Mendelian disorders; however, it has been only recently that the histone proteins themselves have been directly implicated in Mendelian conditions. High throughput sequencing has recently identified mutations in genes encoding histone H1, H3 and H4, all causing neurodevelopmental disorders with clinical variability. Notably, many of the mutations lie outside of recognised post-translational modification-associated residues, suggesting disrupting the core functions of histones is a primary molecular mechanism underpinning these neurodevelopmental phenotypes. In this review, we describe the clinical and genetic features of histone-related disorders, focusing on the unique aspects associated with each histone gene family, while noting the commonalities which provide insight into the required roles for histone fidelity in brain development and functioning.

  • Genetics, Medical

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.