Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells.
Self-renewing embryonic stem (ES) cells have an exceptional need for timely biomass production, yet the transcriptional control mechanisms responsible for meeting this requirement are largely unknown. We report here that Ronin (Thap11), which is essential for the self-renewal of ES cells, binds with its transcriptional coregulator, Hcf-1, to a highly conserved enhancer element that previously lacked a recognized binding factor. The subset of genes bound by Ronin/Hcf-1 function primarily in transcription initiation, mRNA splicing, and cell metabolism; genes involved in cell signaling and cell development are conspicuously underrepresented in this target gene repertoire. Although Ronin/Hcf-1 represses the expression of some target genes, its activity at promoter sites more often leads to the up-regulation of genes essential to protein biosynthesis and energy production. We propose that Ronin/Hcf-1 controls a genetic program that contributes to the unimpeded growth of ES cells.
Dejosez
Marion
M
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Levine
Stuart S
SS
Frampton
Garrett M
GM
Whyte
Warren A
WA
Stratton
Sabrina A
SA
Barton
Michelle C
MC
Gunaratne
Preethi H
PH
Young
Richard A
RA
Zwaka
Thomas P
TP
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004734:Energy Metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D051863:Host Cell Factor C1 / Q000378:metabolism*; D051379:Mice; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D012097:Repressor Proteins; C530078:Thap11 protein, mouse