The H2A.Z-nuclesome code in mammals: emerging functions


Trends in Genomics
Fatima Valdes Mora.jpg
Dr Fatima Valdes Mora, Team Leader, Children's Cancer Institute

A recent publication in Trends in Genomics highlighted Dr. Valdes-Mora's investigation into the functions and role of histone variations in cancers. This helps to define relevant targets not only in DIPG but also other cancers for the next group of trials. This investigation was funded by The Cure Starts Now and the DIPG/DMG Collaborative.

Highlights

  • The histone variant H2A.Z has been involved in many diverse and contrasting functions.
  • H2A.Z complex biology, including different post-translational modifications, isoforms, and nucleosome partners, may explain the conflicting molecular properties associated with H2A.Z, however, how all these molecular layers work together remains unclear.
  • H2A.Z is essential for RNA polymerase II pausing and enhancer activation during transcription, as well as initiation of replication origins, accurate mitotic transition, and repair at DNA damaged sites.
  • H2A.Z is a master regulator for development, cell differentiation, and neural activity; therefore, we predict that future studies will link H2A.Z with a range of neurological and developmental disorders.

H2A.Z is a histone variant that provides specific structural and docking-side properties to the nucleosome, resulting in diverse and specialised molecular and cellular functions. In this review, we discuss the latest studies uncovering new functional aspects of mammalian H2A.Z in gene transcription, including pausing and elongation of RNA polymerase II (RNAPII) and enhancer activity; DNA repair; DNA replication; and 3D chromatin structure. We also review the recently described role of H2A.Z in embryonic development, cell differentiation, neurodevelopment, and brain function. In conclusion, our cumulative knowledge of H2A.Z over the past 40 years, in combination with the implementation of novel molecular technologies, is unravelling an unexpected and complex role of histone variants in gene regulation and disease.

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