Insights into GATA-1-mediated gene activation versus repression via genome-wide chromatin occupancy analysis.
The transcription factor GATA-1 is required for terminal erythroid maturation and functions as an activator or repressor depending on gene context. Yet its in vivo site selectivity and ability to distinguish between activated versus repressed genes remain incompletely understood. In this study, we performed GATA-1 ChIP-seq in erythroid cells and compared it to GATA-1-induced gene expression changes. Bound and differentially expressed genes contain a greater number of GATA-binding motifs, a higher frequency of palindromic GATA sites, and closer occupancy to the transcriptional start site versus nondifferentially expressed genes. Moreover, we show that the transcription factor Zbtb7a occupies GATA-1-bound regions of some direct GATA-1 target genes, that the presence of SCL/TAL1 helps distinguish transcriptional activation versus repression, and that polycomb repressive complex 2 (PRC2) is involved in epigenetic silencing of a subset of GATA-1-repressed genes. These data provide insights into GATA-1-mediated gene regulation in vivo.
Yu
Ming
M
Department of Pediatric Hematology-Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, MA 02115, USA.
Riva
Laura
L
Xie
Huafeng
H
Schindler
Yocheved
Y
Moran
Tyler B
TB
Cheng
Yong
Y
Yu
Duonan
D
Hardison
Ross
R
Weiss
Mitchell J
MJ
Orkin
Stuart H
SH
Bernstein
Bradley E
BE
Fraenkel
Ernest
E
Cantor
Alan B
AB
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001710:Biotin / Q000378:metabolism; D019921:Biotinylation; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D020868:Gene Silencing; D016678:Genome / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D019809:Streptavidin / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D002843:Chromatin; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D001710:Biotin; D019809:Streptavidin