Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-Seq of mouse embryonic stem cells in response to changes in Sall4

ABSTRACT: Sall4 is a stem cell factor which is important for embryogenesis. We have genetically modified Sall4 in mouse embryonic stem cells to access the transcriptional changes. There are three different genetic modifications for the ES cells in the form of Sall4 Knockout (KO), Sall4 Zinc Finger Cluster 4 Mutation (ZFC4mut) and Sall4 Zinc Finger Cluster 4 Deletion (ZFC4Δ) respectively that we have considered for our study.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Kashyap Chhatbar

PROVIDER: E-MTAB-7343 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

SALL4 controls cell fate in response to DNA base composition.

Pantier Raphaël R Chhatbar Kashyap K Quante Timo T Skourti-Stathaki Konstantina K Cholewa-Waclaw Justyna J Alston Grace G Alexander-Howden Beatrice B Lee Heng Yang HY Cook Atlanta G AG Spruijt Cornelia G CG Vermeulen Michiel M Selfridge Jim J Bird Adrian A

Molecular cell 20210105 4

Mammalian genomes contain long domains with distinct average compositions of A/T versus G/C base pairs. In a screen for proteins that might interpret base composition by binding to AT-rich motifs, we identified the stem cell factor SALL4, which contains multiple zinc fingers. Mutation of the domain responsible for AT binding drastically reduced SALL4 genome occupancy and prematurely upregulated genes in proportion to their AT content. Inactivation of this single AT-binding zinc-finger cluster mi ...[more]

PMID: 33406384

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Project description:Embryonic stem cells have potential utility in regenerative medicine due to their pluripotent characteristics. Sall4, a zinc-finger transcription factor, is expressed very early in embryonic development with Oct4 and Nanog, two well characterized pluripotency regulators. Sall4 plays an important role in governing the fate of stem cells through transcriptional regulation of both Oct4 and Nanog. Using chromatin immunoprecipitation coupled to microarray hybridization (ChIP on Chip), we have mapped global gene targets of Sall4 unveiling possible regulation of broad ES cell functions. Approximately 5,000 genes were identified that were bound by the Sall4 protein and many of these have major functions in developmental and regulatory pathways. Sall4 bound more than six times as many annotated genes within promoter regions as Oct4 and twice as many as Nanog. Immunoprecipitation revealed a heterotrimeric protein complex between Sall4, Oct4, and Nanog, consistent with binding site co-occupancies. Further, Sall4 bound many genes that are regulated in part by the chromatin-based epigenetic events mediated by polycomb-repressive complexes and bivalent domains. This suggests that Sall4 plays a central and diverse role in regulating stem cell pluripotency during early embryonic development that involves integration of transcriptional and epigenetic control processes. Keywords: ChIP-chip We used ChIP-chip to map global promoter bound by Sall4, a zinc finger transcription factor. Growing evidence has suggested that Sall4 plays a vital role in ES cell pluripotency maintenance. Evidence for this includes its recent use as a marker for somatic cell reprogramming, in a genetic signature for ES cells, and evidence that Sall4 enhances reprogramming. These recent findings and two previously described interactions with Oct4 and Nanog strongly support the role of Sall4 in ES cells. This hypothesis was furthered here as we show that Sall4 plays important roles through transcriptional regulation of vital ES cell genes.

Dataset Information

RNA-Seq of mouse embryonic stem cells in response to changes in Sall4

Publications

SALL4 controls cell fate in response to DNA base composition.

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