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Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells

ABSTRACT: Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells

PROVIDER: PRJNA335995 | ENA |

REPOSITORIES: ENA

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Dido as a switchboard that regulates self-renewal and differentiation in embryonic stem cells (ChIP-seq)

Project description:Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. Embryonic stem cells (ESC) strongly express Dido3, whose C-terminal truncation impedes ESC differentiation while retaining self-renewal. We show that Dido3 binds to its gene locus via H3K4me3 and RNA pol II and, at differentiation onset, induces expression of its splice variant Dido1, which then leads to Dido3 degradation and downregulation of stemness genes. We propose that Dido isoforms act as a switchboard to regulate genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation.

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MacroH2A1 regulates the balance between self-renewal and differentiation commitment in embryonic and adult stem cells

Project description:One of the most striking epigenetic alterations that occurs at the level of the nucleosome is the complete exchange of the canonical H2A histones for the macroH2A variant. Here, we provide insight in the function of this unique histone variant in embryonic and adult stem cells. Knockdown of macroH2A1 in mouse embryonic stem (mES) cells limited their capacity to differentiate but not their self-renewal. The loss of macroH2A1 interfered with the proper activation of differentiation genes, most of which are direct target genes of macroH2A. Additionally, macroH2A1-deficient mES cells displayed incomplete inactivation of pluripotency genes and formed defective embryoid bodies. In vivo, macroH2A1-deficient teratomas contained a massive expansion of malignant, undifferentiated carcinoma tissue. In the heterogeneous culture of primary human keratinocytes, macroH2A1 levels negatively correlated with the self-renewal capacity of the pluripotent compartment. Together these results establish macroH2A1 as a critical chromatin component that regulates the delicate balance between self-renewal and differentiation of embryonic and adult stem cells. Examination of the histone variant macroH2A1 in mouse Embryonic stem cells

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Project description:This SuperSeries is composed of the following subset Series: GSE25265: Genome-wide analysis of the binding pattern of the transcriptional co-activator Cbp. GSE25268: The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells Refer to individual Series

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