ATP-binding cassette protein ABCF1 couples transcription and genome surveillance in embryonic stem cells through low-complexity domain

Choi, Eun-Bee; Vodnala, Munender; Zerbato, Madeleine; Wang, Jianing; Ho, Jaclyn J.; Inouye, Carla; Ding, Lai; Fong, Yick W.

doi:10.1126/sciadv.abk2775

Cited by 5 publications

(15 citation statements)

References 52 publications

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“…We surmise that it could be due to the low expression level of SOX15 (see Figure 1B) and the often weak and transient nature of functional coactivator-activator interactions (31) Therefore, we tested SOX15-SCCs interactions by performing transient transfection and coimmunoprecipitation in 293T cells. We found that SOX15, like SOX2, binds XPC, DKC1, and ABCF1 (Figure 1E) (13, 15, 32, 33). Together with our previous observations that SCCs are recruited to SOX15-target genes including Nanog , Oct4 , and Sox2 in mouse ESCs (12, 13, 15), we propose that SOX15 activates stem cell-specific transcription by cooperating with SCCs through direct recruitment.…”

Section: Resultsmentioning

confidence: 91%

“…We have previously shown that transcriptional activation by SOX2 and OCT4 requires three stem cell coactivators (SCCs) present in P1M fraction, namely, the XPC DNA repair complex, the dyskerin (DKC1) ribonucleoprotein complex, and the ATP-binding cassette subfamily F member 1 (ABCF1) (12, 13, 15). We therefore asked whether SOX15 also potentiates transcription by cooperating with SCCs.…”

Section: Resultsmentioning

confidence: 99%

“…Untagged human DKC1 cDNA was subcloned into pHAGE-IRES-Neo. Mammalian expression constructs for untagged XPC-RAD23B-CETN2 complex (pHAGE-XPC.com) (12) and V5-tagged ABCF1 (pFLAG-CMV5a-ABCF1-V5) (15) were described. Note that the V5 tag followed by a translation stop codon was inserted upstream of the built-in C-terminal FLAG tag in pFLAG-CMV5a vector.…”

Section: Methodsmentioning

confidence: 99%

“…The human NANOG transcription template, purification of activators OCT4 and SOX TFs, general transcription factors, RNA polymerase II, recombinant XPC complex and DKC1 complexes reconstituted from insect Sf9 cells (12, 13), and recombinant ABCF1 purified from Escherichia coli (15) were described. Partially-purified phosphocelluose 1M (P1M) nuclear cell extracts from NT2 cells were described (12).…”

Section: Methodsmentioning

confidence: 99%

“…In embryonic stem cells (ESCs), SOX2 along with TFs OCT4 and NANOG activates a core regulatory network that is essential for stem cell self-renewal and pluripotency (7)(8)(9)(10)(11). SOX2 activates transcription by recruiting OCT4 and stem cell-enriched coactivators to gene enhancers containing sox-oct sequence motifs (12)(13)(14)(15). The central role of SOX2 in reprogramming somatic cells to induced pluripotent stem cells (iPSCs) further highlights the importance of SOX2 in pluripotency (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

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SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

Choi

Saini

Zerbato

et al. 2022

Preprint

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SOX2 and SOX15 are Sox family transcription factors enriched in embryonic stem cells (ESCs). The role of SOX2 in activating gene expression programs essential for stem cell self-renewal and acquisition of pluripotency during somatic cell reprogramming is well-documented. However, the contribution of SOX15 to these processes is unclear and often presumed redundant with SOX2 largely because overexpression of SOX15 can partially restore self-renewal in SOX2-deficient ESCs. Here, we show that SOX15 contributes to stem cell maintenance by cooperating with ESC-enriched transcriptional coactivators to ensure optimal expression of pluripotency-associated genes. We demonstrate that SOX15 depletion compromises reprogramming of fibroblasts to pluripotency which cannot be compensated by SOX2. Ectopic expression of SOX15 promotes the reversion of a post-implantation, epiblast stem cell state back to a pre-implantation, ESC-like identity even though SOX2 is expressed in both cell states. We also uncover a role of SOX15 in lineage specification, by showing that loss of SOX15 leads to defects in commitment of ESCs to neural fates. SOX15 promotes neural differentiation by binding to and activating a previously uncharacterized distal enhancer of a key neurogenic regulator, Hes5. Together, these findings identify a multifaceted role of SOX15 in induction and maintenance of pluripotency and neural differentiation.

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

Choi

Saini

Zerbato

et al. 2022

Preprint

Self Cite

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Transcription factor SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating the neurogenic gene Hes5

Choi¹,

Vodnala²,

Saini³

et al. 2023

Journal of Biological Chemistry

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TNF-α and Poly(I:C) induction of A20 and activation of NF-κB signaling are independent of ABCF1 in human airway epithelial cells

Cao,

Ishak,

Shpilman

et al. 2023

Sci Rep

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ABCF1 is the most characterized member of the ABCF family in eukaryotes with proposed functions related to innate immunity in fibroblasts, macrophages, and epithelial cells. Currently, a mechanistic link between ABCF1 and immune responses in human airway epithelial cells (HAECs) remains to be clearly defined. The present study aimed at characterizing the function of ABCF1 in the context of nuclear factor nuclear factor κB (NF-κB) mediated pro-inflammatory responses in an immortalized human airway epithelial cell line, HBEC-6KT. We demonstrated that with ABCF1 silencing under basal conditions, TNF Alpha Induced Protein 3 (TNFAIP3/A20) protein expression and downstream expression and activation of transcription factors, NF-κB and Interferon regulatory factor 3 (IRF-3), were not disrupted. We followed with investigations of ABCF1 function under a pro-inflammatory stimuli that are known to be regulated by A20. We demonstrated that under Polyinosinic:polycytidylic acid (Poly(I:C)) and tumor Necrosis Factor-α (TNF-α) challenge with ABCF1 silencing, there was a significant reduction in secreted levels of interleukin-8 (IL-8) and a trend for reduced IL-6. However, we observed no changes to the expression levels of A20 and the activation status of the transcription factors, NF-κB and IRF-3. Collectively, these studies demonstrate that Poly(I:C) and TNF-α induced IL-8 is regulated by ABCF1 via pathways independent of NF-κB and IRF-3 activation.

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ATP-binding cassette protein ABCF1 couples transcription and genome surveillance in embryonic stem cells through low-complexity domain

Abstract: DNA sensor ABCF1 links genome surveillance to pluripotency gene transcription in embryonic stem cells.

Cited by 5 publications

References 52 publications

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating Hes5

Transcription factor SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating the neurogenic gene Hes5

TNF-α and Poly(I:C) induction of A20 and activation of NF-κB signaling are independent of ABCF1 in human airway epithelial cells

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