A new twist to Sin3 complexes in pluripotent cells

Pantier, Raphaël; Mullin, Nicholas P.; Chambers, Ian

doi:10.15252/embj.201797516

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…To test our hypothesis, the interaction between LINC00941 and the NuRD complex was subsequently further verified. Because multiple components of the NuRD complex such as RBBP4, RBBP7, and HDAC2 can also function as subunits of other multiprotein complexes, including Sin3, Extra Sex Combs/Enhancer of Zeste (ESC/E[Z]), and nucleosome remodeling factor (NURF) complex ( Dubey et al, 2017 ; Pantier et al, 2017 ; Zahid et al, 2021 ), we focused our experiments on MTA2, a core subunit of the NuRD complex ( Low et al, 2020 ). The binding of in vitro–transcribed, biotinylated LINC00941 and NuRD-associated MTA2 from a cell lysate with subsequent RNA pull-down was confirmed by Western blot analysis ( Fig 1C ).…”

Section: Resultsmentioning

confidence: 99%

lncRNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation

Morgenstern,

Molthof,

Schwartz

et al. 2024

Life Sci. Alliance

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Numerous long non-coding RNAs (lncRNAs) were shown to have a functional impact on cellular processes such as human epidermal homeostasis. However, the mechanism of action for many lncRNAs remains unclear to date. Here, we report that lncRNA LINC00941 regulates keratinocyte differentiation on an epigenetic level through association with the NuRD complex, one of the major chromatin remodelers in cells. We find that LINC00941 interacts with NuRD-associated MTA2 and CHD4 in human primary keratinocytes. LINC00941 perturbation changes MTA2/NuRD occupancy at bivalent chromatin domains in close proximity to transcriptional regulator genes, including theEGR3gene coding for a transcription factor regulating epidermal differentiation. Notably, LINC00941 depletion resulted in reduced NuRD occupancy at theEGR3gene locus, increased EGR3 expression in human primary keratinocytes, and increased abundance of EGR3-regulated epidermal differentiation genes in cells and human organotypic epidermal tissues. Our results therefore indicate a role of LINC00941/NuRD in repressing EGR3 expression in non-differentiated keratinocytes, consequentially preventing premature differentiation of human epidermal tissues.

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Section: Resultsmentioning

confidence: 99%

lncRNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation

Morgenstern,

Molthof,

Schwartz

et al. 2024

Life Sci. Alliance

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“…2C-D ), demonstrating its dual functional capacity in molecular interactions. However, AP-MS analysis falls short in determining the direct binding partners of FAM60A within the Sin3/HDAC complex, particularly its interaction with SIN3A, the scaffold protein within the SIN3/HDAC complex 30,31 . To address this limitation, our research extends beyond proteomic analysis, using gel-filtration chromatography coupled with cross-linking proteomics.…”

Section: Discussionmentioning

confidence: 99%

Beyond the Sin3/HDAC Complex: FAM60A emerges as a regulator of RNA Splicing

Huda,

Zimmermann,

Nagar

et al. 2024

Preprint

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FAM60A, traditionally linked to chromatin remodeling within the Sin3/HDAC complex, has emerged as a critical regulator in RNA splicing. Employing an integrative approach that combines immunological assays, CRISPR/Cas9 technology, comprehensive genomics, proteomics, and advanced cross-linking mass spectrometry, complemented by sophisticated 3D molecular modeling, our study challenges and extends the existing understanding of FAM60A functional dynamics. Contravening previous perceptions, our findings elucidate that FAM60A does not interact directly with SIN3A, rather establishes direct interactions with SAP30 and HDAC1, redefining its relationship with the Sin3/HDAC complex. These interactions, deciphered through detailed 3D structural analysis supported by cross-linking constraints, signify a complex architectural role of FAM60A within chromatin remodeling processes. Moreover, our research unveils FAM60A pivotal role in RNA processing, particularly in splicing regulation. Through extensive molecular interactions with a diverse array of mRNA-binding proteins and principal spliceosome components, FAM60A emerges as a key regulator of RNA splicing. This expanded role delineates its influence on gene expression regulation, spotlighting its capacity to modulate critical cellular processes. In sum, this study unveils FAM60A key role in gene regulation and RNA splicing, and suggests new paths for cellular and therapeutic research.

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“…FAM60A, a subunit of the SIN3A/HDAC complex, is a cell cycle regulatory protein with a key role in the division of malignant tumors 9 . The downregulation of its expression in esophageal cancer cells has been found to reduce the number of G1 phase cells, prevent the entry of cells into the G2/M phase, inhibit cell proliferation, promote apoptosis, and inhibit metastasis and invasion in vitro 12,33,34 . Moreover, H. pylori infection was reported to increase the ratio of gastric cancer cells in the S phase and reduce the proportion of those in the G1/G0 phase; the knockdown of FAM60A expression rescued this phenotype and ultimately caused G1/G0 phase arrest 17,25 .…”

Section: Discussionmentioning

confidence: 99%

“… 9 The downregulation of its expression in esophageal cancer cells has been found to reduce the number of G1 phase cells, prevent the entry of cells into the G2/M phase, inhibit cell proliferation, promote apoptosis, and inhibit metastasis and invasion in vitro. 12 , 33 , 34 Moreover, H. pylori infection was reported to increase the ratio of gastric cancer cells in the S phase and reduce the proportion of those in the G1/G0 phase; the knockdown of FAM60A expression rescued this phenotype and ultimately caused G1/G0 phase arrest. 17 , 25 Some scholars have pointed out that FAM60A can act as a tumor promoter in pancreatic cancer and mediate malignant behaviors such as proliferation and invasion.…”

Section: Discussionmentioning

confidence: 99%

FAM60A promotes osteosarcoma development and progression

et al. 2023

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BackgroundOsteosarcoma (OS) is a highly malignant primary bone tumor. Family of homology 60A (FAM60A) reportedly contributes to the malignant growth of some tumors.MethodsHerein we investigated the mRNA expression level of FAM60A by combining OS and non‐cancer samples from public databases. Immunohistochemistry was performed to determine protein expression levels of FAM60A in patients with OS. Further, RT‐qPCR and western blotting were conducted to evaluate FAM60A expression in various OS cell lines. CCK‐8 assay, colony formation assay, and flow cytometry were applied to determine the function of FAM60A. Finally, functional enrichment analysis was performed based on FAM60A co‐expressed genes.ResultsFAM60A mRNA expression level was found to be significantly upregulated (standardized mean difference = 1.27, 95% CI [0.67–1.88]). Survival analyses suggested that higher expression of FAM60A was indicative of poor prognoses. Similarly, FAM60A protein expression level was also observed to be upregulated. Knocking down FAM60A expression inhibited OS cell proliferation, increased apoptosis, and blocked cells from entering the S phase. Besides, cell cycle was the most prominently enriched pathway, and BUB1, DTL, and EXO1 were identified as hub genes.ConclusionsFAM60A expression was found to be markedly upregulated in OS; furthermore, FAM60A was observed to promote OS cell proliferation, inhibit apoptosis, and participate in cell cycle regulation. Besides, FAM60A may interact with hub genes to participate in the progress of OS.

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A new twist to Sin3 complexes in pluripotent cells

Cited by 8 publications

References 11 publications

lncRNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation

lncRNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation

Beyond the Sin3/HDAC Complex: FAM60A emerges as a regulator of RNA Splicing

FAM60A promotes osteosarcoma development and progression

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