Genetic Determinants and Epigenetic Effects of Pioneer-factor Occupancy

Overview

Journal Nat Genet

Specialty Genetics

Date 2018 Jan 24

PMID 29358654

Citations 97

Authors

Julie Donaghey

Sudhir Thakurela

Jocelyn Charlton

Jennifer S Chen

Zachary D Smith

Hongcang Gu

Ramona Pop

Kendell Clement

Elena K Stamenova

Rahul Karnik

David R Kelley

Casey A Gifford

Davide Cacchiarelli

John L Rinn

Andreas Gnirke

Michael J Ziller

Alexander Meissner

Affiliations

Soon will be listed here.

Abstract

Transcription factors (TFs) direct developmental transitions by binding to target DNA sequences, influencing gene expression and establishing complex gene-regultory networks. To systematically determine the molecular components that enable or constrain TF activity, we investigated the genomic occupancy of FOXA2, GATA4 and OCT4 in several cell types. Despite their classification as pioneer factors, all three TFs exhibit cell-type-specific binding, even when supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be distinguished by low enrichment at loci that are highly occupied by these factors in alternative cell types. We find that expression of additional cofactors increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and changes to DNA accessibility can occur in G-arrested cells, but subsequent loss of DNA methylation requires DNA replication.

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