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Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle

ABSTRACT: Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle

PROVIDER: PRJNA1143411 | ENA |

REPOSITORIES: ENA

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Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle (RNA-seq)

Project description:SETD1A catalyzes methylation of histone 3 lysine 4 (H3K4) and plays a critical role in development of multiple cancers. The abrrent expression of SETD1A relates to poor prognosis of gastric cancer (GC) patients. Here, we revealed that SETD1A is required for GC cell proliferation. Rescue experiment showed catalytic function is not necessary for GC cell growth and gene expression, whereas a novel non-catalytic FLOS domain is indispensable. The CRISPR screening targeting SETD1A targets identified that TAF6 acts as a downstream target of SETD1A which is essential for GC cell survival. Both SETD1A and TAF6 are required for G1/S cell cycle progression in GC cells. Non-catalytic component of SETD1A regulating expression of TAF6 through coactivating with E2F4s. These results demonstrate that non-canonical roles of SETD1A in GC cell, which supplys a potential therapeutic opportunity for GC.

2025-07-25 | GSE273825 | GEO

Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle (ChIP-seq)

2025-07-25 | GSE273824 | GEO

Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle (ChIP-seq)

Project description:Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle (ChIP-seq)

| PRJNA1143421 | ENA

Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-07-25 | GSE273826 | GEO

SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [RNA-seq]

Project description:The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through its non-catalytic FLOS domain mediated recruitment of cyclin K and regulation of DNA damage response genes. In this study, we identify a functional nuclear localization signal and interaction partners for the FLOS domain. Our proteomics analysis against FLOS domain-binding partners reveals that the SETD1A FLOS domain binds mitosis-associated proteins BuGZ/BUB3. Targeted inhibition of both cyclin K and BuGZ/BUB3 binding motifs on SETD1A shows synergistic anti-leukemic effects. BuGZ/BUB3 localize to SETD1A-positive promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions adjacent to SETD1A-target genes. The GLEBS motif and intrinsically disordered region of BuGZ are required for both SETD1A binding and the leukemia cell proliferation. Despite the role of BuGZ/BUB3 at mitotic phase, the cell-cycle specific SETD1A restoration study indicates the roles of SETD1A at G1/S phase of cell cycle. Discovery of this complex indicates the indispensable role of the SETD1A-BuGZ axis in cancer.

2023-07-29 | GSE159145 | GEO

SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [ChIP-seq]

2023-07-29 | GSE159144 | GEO

TRANSCRIPTIONAL ACTIVATION BY E2F4 INDEPENDENT OF THE RB FAMILY

Project description:E2F transcription factors are central regulators of cell cycle progression and cell fate decisions in mammalian cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. E2F4 often represents the predominant E2F activity in cells. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. Importantly, this role for E2F4 is completely independent of the RB family. Accordingly, an unbiased analysis of the E2F4 interactome shows that E2F4 functionally interacts with chromatin regulators associated with gene activation in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that reveal novel insights into the biology of rapidly dividing cell types.

2019-04-26 | PXD008796 | Pride

A non-catalytic function of SETD1A regulates Cyclin K and the DNA damage response [RNA-seq]

Project description:MLL/SET methyltransferases catalyze methylation of histone 3 lysine 4 and play critical roles in development and cancer. We assessed MLL/SET proteins and found that SETD1A is required for survival of acute myeloid leukemia (AML) cells. Mutagenesis studies and CRISPR-Cas9 domain screening, showed the enzymatic SET domain is not necessary for AML cell survival but that a newly identified region, termed the FLOS (Functional Location on SETD1A) domain, is indispensable. FLOS disruption suppresses DNA damage response genes and induces p53-dependent apoptosis. The FLOS domain acts as a Cyclin K-binding site that is required for chromosomal recruitment of Cyclin K, and for DNA repair-associated gene expression in S phase. These data identify a connection between the chromatin regulator SETD1A and the DNA damage response that is independent of histone methylation, and suggests that targeting SETD1A and Cyclin K complexes may represent a therapeutic opportunity for AML and potentially other cancers.

2018-02-01 | GSE108614 | GEO

E2F4 wt and knockout neurospheres

Project description:E2F4 wild and knockout type neurospheres from E12.5 forebrain. E2F4 transcription factor regulates the expression of the genes which are required for neural stem cell expansion in the developing mouse brain. The results of microarray analysis will help to identify the signaling pathways affected by E2F4 deletion and refine the neural stem cell regulatory mechanism. Keywords: other

2008-02-13 | GSE10401 | GEO

IPs of SETD1A COMPASS-HUMAN LC-MSMS

Project description:Mapping physical interactions of SETD1A COMPOASS in HEK293T cells using endogenous immunoprecipitation followed by label-free quantitative proteomics. We found a novel protein interacts with SETD1A, which is RAD18 (DNA damage repair protein).

2019-06-13 | PXD012549 | Pride

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