Genetic determinants and epigenetic effects of pioneer-factor occupancy

被引:118
作者
Donaghey, Julie [1 ,2 ]
Thakurela, Sudhir [1 ,2 ]
Charlton, Jocelyn [2 ,3 ]
Chen, Jennifer S. [2 ]
Smith, Zachary D. [1 ,2 ]
Gu, Hongcang [1 ]
Pop, Ramona [2 ]
Clement, Kendell [1 ,2 ]
Stamenova, Elena K. [1 ]
Karnik, Rahul [1 ,2 ]
Kelley, David R. [2 ]
Gifford, Casey A. [1 ,2 ,5 ]
Cacchiarelli, Davide [1 ,2 ,6 ]
Rinn, John L. [1 ,2 ,7 ]
Gnirke, Andreas [1 ]
Ziller, Michael J. [4 ]
Meissner, Alexander [1 ,2 ,3 ]
机构
[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[2] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
[3] Max Planck Inst Mol Genet, Dept Genome Regulat, Berlin, Germany
[4] Max Planck Inst Psychiat, Dept Translat Psychiat, Munich, Germany
[5] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA
[6] Telethon Inst Genet & Med TIGEM, Armenise Harvard Lab Integrat Genom, Pozzuoli, Italy
[7] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA
关键词
TRANSCRIPTION FACTOR FOXA; EMBRYONIC STEM-CELLS; DNA DEMETHYLATION; GUT ENDODERM; DEVELOPMENTAL COMPETENCE; REGULATORY ELEMENTS; COMPACTED CHROMATIN; MAMMALIAN LIVER; CHIP-SEQ; IN-VITRO;
D O I
10.1038/s41588-017-0034-3
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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(1)-arrested cells, but subsequent loss of DNA methylation requires DNA replication.
引用
收藏
页码:250 / +
页数:11
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