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IWS1 Stimulates Pol II Transcription Elongation In Vivo (revision data)

ABSTRACT: The protein IWS1 (Interacts with SPT6 1) has been implicated in various transcription-associated processes, but whether it has a direct role in RNA polymerase (Pol) II transcription remains unclear. Here, we establish a rapid depletion system for IWS1 in human cells, and use it to elucidate its function in vivo by multi-omics kinetic analysis. We show that IWS1 depletion results in a global decrease of RNA synthesis in vivo that is due to a decrease in Pol II elongation velocity and in vitro biochemical assays reveal that IWS1 directly stimulates Pol II transcription by lowering the nucleosome entry barrier. Further analyses show that H3K36me3 decreases upon IWS1 depletion although the recruitment of the histone methyltransferase SETD2 to chromatin is unaffected. We conclude that IWS1 has a direct role in Pol II transcription and is essential for maintaining normal RNA elongation, which in turn is required for normal chromatin methylation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Bone Marrow

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Yumeng Yan

LAB HEAD: Henning Urlaub

PROVIDER: PXD066658 | Pride | 2025-07-30

REPOSITORIES: Pride

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			Action	DRS
	DIANN_output.zip	Other
	UP000005640_9606_20240327.fasta	Fasta
	Y_Yan_A_Zheenbekova_090425_110425Expl3_DMSO_R1.raw	Raw
	Y_Yan_A_Zheenbekova_090425_110425Expl3_DMSO_R2.raw	Raw
	Y_Yan_A_Zheenbekova_090425_110425Expl3_DMSO_R3.raw	Raw

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IWS1 Stimulates Pol II Transcription Elongation In Vivo

Project description:The protein IWS1 (Interacts with SPT6 1) has been implicated in various transcription-associated processes, but whether it has a direct role in RNA polymerase (Pol) II transcription remains unclear. Here, we establish a rapid depletion system for IWS1 in human cells, and use it to elucidate its function in vivo by multi-omics kinetic analysis. We show that IWS1 depletion results in a global decrease of RNA synthesis in vivo that is due to a decrease in Pol II elongation velocity and in vitro biochemical assays reveal that IWS1 directly stimulates Pol II transcription by lowering the nucleosome entry barrier. Further analyses show that H3K36me3 decreases upon IWS1 depletion although the recruitment of the histone methyltransferase SETD2 to chromatin is unaffected. We conclude that IWS1 has a direct role in Pol II transcription and is essential for maintaining normal RNA elongation, which in turn is required for normal chromatin methylation.

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