Format

Send to

Choose Destination
Nat Genet. 2018 Feb;50(2):250-258. doi: 10.1038/s41588-017-0034-3. Epub 2018 Jan 22.

Genetic determinants and epigenetic effects of pioneer-factor occupancy.

Author information

1
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
3
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
4
Gladstone Institute for Cardiovascular Disease, San Francisco, CA, USA.
5
Armenise-Harvard Laboratory of Integrative Genomics, Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
6
BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
7
Department for Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
8
Broad Institute of MIT and Harvard, Cambridge, MA, USA. meissner@molgen.mpg.de.
9
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. meissner@molgen.mpg.de.
10
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany. meissner@molgen.mpg.de.

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 G1-arrested cells, but subsequent loss of DNA methylation requires DNA replication.

Comment in

PMID:
29358654
PMCID:
PMC6517675
DOI:
10.1038/s41588-017-0034-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center