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Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network (2)

ABSTRACT: The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. It remains unclear whether interactions. Here we show that a core member of the Set/MLL complex, WDrepeat protein-5 (Wdr5), is a novel regulator of self-renewal and partners with Oct4 to maintain an intact transcriptional network and for efficient formation of induced pluripotent stem (iPS) cells. Moreover, we provide evidence that Oct4 interacts with chromatin components and is indispensible for epigenetic regulation. These findings suggest an integrated transcriptional and epigenetic model, mediated through Wdr5, for the maintenance of ES cell self-renewal and somatic cell reprogramming. Differential gene expressions upon down-regulation of Wdr5 was analysed by comparing Wdr5R4 –dox (triplicate) and LucR +dox (duplicate) RNA samples Gene expression changes upon down-regulation of Oct4 was analysed by comparing Oct4 shRNA (duplicate) and GFP shRNA (duplicate) after 4day transfection Wdr5: 5 samples are analyzed: Luciferase (Luc, 2 replicates) and Wdr5 with no dox (minusDox, 3 replicates) Oct4-GFP: 4 samples are analyzed: Oct4 shRNA (Oct4, 2 replicates) and GFP shRNA (GFP, 2 replicates)

ORGANISM(S): Mus musculus

SUBMITTER: Jonathan Monk

PROVIDER: E-GEOD-19588 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network (2)

Project description:The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. It remains unclear whether interactions. Here we show that a core member of the Set/MLL complex, WDrepeat protein-5 (Wdr5), is a novel regulator of self-renewal and partners with Oct4 to maintain an intact transcriptional network and for efficient formation of induced pluripotent stem (iPS) cells. Moreover, we provide evidence that Oct4 interacts with chromatin components and is indispensible for epigenetic regulation. These findings suggest an integrated transcriptional and epigenetic model, mediated through Wdr5, for the maintenance of ES cell self-renewal and somatic cell reprogramming. Differential gene expressions upon down-regulation of Wdr5 was analysed by comparing Wdr5R4 –dox (triplicate) and LucR +dox (duplicate) RNA samples Gene expression changes upon down-regulation of Oct4 was analysed by comparing Oct4 shRNA (duplicate) and GFP shRNA (duplicate) after 4day transfection

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Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network

Project description:The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. However, it remains unclear whether components of these networks functionally interact and if so, what factors mediate such interactions. Here we show that WD-repeat protein-5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a novel regulator of ES cell self-renewal. We demonstrate that Wdr5, an ‘effector’ of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. In concordance, genome-wide ChIP-Seq and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. We show that the Oct4-Sox2-Nanog circuitry cooperates with trxG for transcriptional activation of key self-renewal regulators. Furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. Collectively, these findings implicate an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming. 7 Samples

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