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ABSTRACT: Flos Lonicerae and Radix Scutellariae extracts

PROVIDER: PRJNA750729 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15296600_1.fastq.gz	Fastqsanger.gz
	SRR15296600_2.fastq.gz	Fastqsanger.gz
	SRR15296601_1.fastq.gz	Fastqsanger.gz
	SRR15296601_2.fastq.gz	Fastqsanger.gz
	SRR15296602_1.fastq.gz	Fastqsanger.gz

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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.

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