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Tousled-like kinase activity is required for transcriptional silencing and suppression of innate immune signaling [ChIP-Seq]

ABSTRACT: Tousled-like kinase activity is required for transcriptional silencing and suppression of innate immune signaling [ChIP-Seq]

PROVIDER: PRJNA542334 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9040810.fastq.gz	Fastqsanger.gz
	SRR9040803.fastq.gz	Fastqsanger.gz
	SRR9040804.fastq.gz	Fastqsanger.gz
	SRR9040805.fastq.gz	Fastqsanger.gz
	SRR9040806.fastq.gz	Fastqsanger.gz

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Tousled-like kinase activity is required for transcriptional silencing and suppression of innate immune signaling

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Tousled-like kinase activity is required for transcriptional silencing and suppression of innate immune signaling [U2OS ATAC-Seq]

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Project description:Tousled-like kinase activity is required for transcriptional silencing and suppression of innate immune signaling [HeLa ATAC-Seq]

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Tousled-like kinase activity is required for transcriptional silencing and suppression of innate immune signaling [ChIP-Seq]

Project description:The Tousled like kinases 1 and 2 (TLK1/2) control histone deposition through the ASF1 histone chaperones and are regulated by the DNA damage response. Depletion of TLK activity caused replication stress, increased chromosomal instability and cell arrest or death. Here, we show that stalled forks in TLK depleted cells are processed by BLM, SAMHD1 and the MRE11 nuclease to generate ssDNA and activate checkpoint signaling. TLK depletion also impaired heterochromatin maintenance, inducing features of alternative lengthening of telomeres and increasing spurious expression of other repetitive elements, associated with impaired deposition of the histone variant H3.3. TLK depletion culminated in a BLM-dependent, STING-mediated innate immune response. In many human cancers, TLK1/2 expression correlated with signatures of chromosomal instability and anti-correlated with STING and innate and adaptive immune response signatures. Together, our results show that TLK activity protects replication forks from active processing, contributes to chromatin silencing and suppresses innate immune responses, suggesting that TLK amplification may protect chromosomally unstable cancers from immune detection.

2020-07-21 | GSE131021 | GEO