Trends Genet 2017 08 29;33(8):566-578. Epub 2017 Jun 29.
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA; Cell and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address:
Covalent histone modifications play an essential role in gene regulation and cellular specification required for multicellular organism development. Monoubiquitination of histone H2A (H2AUb1) is a reversible transcriptionally repressive mark. Exchange of histone H2A monoubiquitination and deubiquitination reflects the succession of transcriptional profiles during development required to produce cellular diversity from pluripotent cells. Germ-line pathogenic variants in components of the H2AUb1 regulatory axis are being identified as the genetic basis of congenital neurodevelopmental disorders. Here, we review the human genetics findings coalescing on molecular mechanisms that alter the genome-wide distribution of this histone modification required for development.