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FACT regulates pluripotency through proximal and distal regulation of gene expression in murine embryonic stem cells

Klein, David C ; Lardo, Santana M ; McCannell, Kurtis N ; Hainer, Sarah J

BMC biology, 2023-08, Vol.21 (1), p.167-167, Article 167 [Periódico revisado por pares]

England: BioMed Central Ltd

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Título:
FACT regulates pluripotency through proximal and distal regulation of gene expression in murine embryonic stem cells
Autor: Klein, David C ; Lardo, Santana M ; McCannell, Kurtis N ; Hainer, Sarah J
Assuntos: Analysis ; Animals ; Binding sites ; Cancer ; Care and treatment ; Cell fate ; Cell growth ; Chromatin ; Chromatin - metabolism ; Clonal deletion ; Deoxyribonuclease ; Depletion ; DNA binding proteins ; Embryo cells ; Embryonic stem cells ; Embryonic Stem Cells - metabolism ; Enhancers ; FACT ; Fibroblasts ; Gene expression ; Gene Expression Regulation ; Genomes ; Histone chaperone ; Histones ; Histones - genetics ; Localization ; Mammals - genetics ; Mice ; Nucleosomes ; Oct-4 protein ; Octamer Transcription Factor-3 - genetics ; Octamer Transcription Factor-3 - metabolism ; Pluripotency ; Proteins ; Regulatory mechanisms (biology) ; RNA polymerase ; Stem cells ; Transcription ; Transcription factors
É parte de: BMC biology, 2023-08, Vol.21 (1), p.167-167, Article 167
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: The FACT complex is a conserved histone chaperone with critical roles in transcription and histone deposition. FACT is essential in pluripotent and cancer cells, but otherwise dispensable for most mammalian cell types. FACT deletion or inhibition can block induction of pluripotent stem cells, yet the mechanism through which FACT regulates cell fate decisions remains unclear. To explore the mechanism for FACT function, we generated AID-tagged murine embryonic cell lines for FACT subunit SPT16 and paired depletion with nascent transcription and chromatin accessibility analyses. We also analyzed SPT16 occupancy using CUT&RUN and found that SPT16 localizes to both promoter and enhancer elements, with a strong overlap in binding with OCT4, SOX2, and NANOG. Over a timecourse of SPT16 depletion, nucleosomes invade new loci, including promoters, regions bound by SPT16, OCT4, SOX2, and NANOG, and TSS-distal DNaseI hypersensitive sites. Simultaneously, transcription of Pou5f1 (encoding OCT4), Sox2, Nanog, and enhancer RNAs produced from these genes' associated enhancers are downregulated. We propose that FACT maintains cellular pluripotency through a precise nucleosome-based regulatory mechanism for appropriate expression of both coding and non-coding transcripts associated with pluripotency.
Editor: England: BioMed Central Ltd
Idioma: Inglês

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FACT regulates pluripotency through proximal and distal regulation of gene expression in murine embryonic stem cells

Klein, David C ; Lardo, Santana M ; McCannell, Kurtis N ; Hainer, Sarah J

England: BioMed Central Ltd

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