Michael H Kagey

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Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that(More)
Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call(More)
Embryonic stem (ES) cells have a unique regulatory circuitry, largely controlled by the transcription factors Oct4, Sox2, and Nanog, which generates a gene expression program necessary for pluripotency and self-renewal. How external signals connect to this regulatory circuitry to influence ES cell fate is not known. We report here that a terminal component(More)
Transcription factors that play key roles in regulating embryonic stem (ES) cell state have been identified, but the chromatin regulators that help maintain ES cells are less well understood. A high-throughput shRNA screen was used to identify novel chromatin regulators that influence ES cell state. Loss of histone H3 Lys 9 (H3K9) methyltransferases,(More)
Control of gene expression during development requires the concerted action of sequence-specific transcriptional regulators and epigenetic modifiers, which are spatially coordinated within the nucleus through mechanisms that are poorly understood. Here we show that transcriptional repression by the Msx1 homeoprotein in myoblast cells requires the(More)
Insulin is capable of regulating cellular and metabolic processes as well as gene expression. In recent years, enthusiasm has surfaced for using insulin-mimetics to study the mechanism of action of insulin. Vanadate and selenate are two compounds that have been found to mimic the action of insulin on control of blood glucose levels in vivo. Vanadate has(More)
Pc2 is a polycomb protein, which has SUMO E3 activity for the corepressors CtBP and CtBP2. Here we demonstrate that, in vivo, Pc2 adapter function contributes to enhancement of CtBP sumoylation. Mutation of the CtBP binding site on Pc2 abolishes E3 activity toward CtBP. However, a carboxyl-terminal fragment of Pc2 that recruits both Ubc9 and CtBP lacks E3(More)
BACKGROUND Modification of proteins by the small ubiquitin like modifier (SUMO) is an essential process in mammalian cells. SUMO is covalently attached to lysines in target proteins via an enzymatic cascade which consists of E1 and E2, SUMO activating and conjugating enzymes. There is also a variable requirement for non-enzymatic E3 adapter like proteins,(More)
Pc2 (Cbx4) is a member of the chromobox family of polycomb proteins, and is a SUMO E3 ligase for the transcriptional corepressor CtBP1. Here, we show that both CtBP1 and Pc2 are phosphorylated by the kinase Akt1, which is activated by growth factor signaling via the PI3-kinase pathway. In the presence of Pc2, phosphorylation of CtBP1 is increased, and this(More)