Autism risk gene POGZ promotes chromatin accessibility and expression of clustered synaptic genes

Eirene Markenscoff-Papadimitriou, Fadya Binyameen, Sean Whalen, James Price, Kenneth Lim, Athena R. Ypsilanti, Rinaldo Catta-Preta, Emily Ling Lin Pai, Xin Mu, Duan Xu, Katherine S. Pollard, Alex S. Nord, Matthew W. State, John L. Rubenstein

Research output: Contribution to journalArticlepeer-review


Deleterious genetic variants in POGZ, which encodes the chromatin regulator Pogo Transposable Element with ZNF Domain protein, are strongly associated with autism spectrum disorder (ASD). Although it is a high-confidence ASD risk gene, the neurodevelopmental functions of POGZ remain unclear. Here we reveal the genomic binding of POGZ in the developing forebrain at euchromatic loci and gene regulatory elements (REs). We profile chromatin accessibility and gene expression in Pogz−/− mice and show that POGZ promotes the active chromatin state and transcription of clustered synaptic genes. We further demonstrate that POGZ forms a nuclear complex and co-occupies loci with ADNP, another high-confidence ASD risk gene, and provide evidence that POGZ regulates other neurodevelopmental disorder risk genes as well. Our results reveal a neurodevelopmental function of an ASD risk gene and identify molecular targets that may elucidate its function in ASD.

Original languageEnglish (US)
Article number110089
JournalCell Reports
Issue number10
StatePublished - Dec 7 2021

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Autism risk gene POGZ promotes chromatin accessibility and expression of clustered synaptic genes'. Together they form a unique fingerprint.

Cite this