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TEAD1 condensates are transcriptionally inactive storage sites on the pericentromeric heterochromatin

ABSTRACT: TEA domain transcription factor 1 (TEAD1), a Hippo pathway transcription factor important in cellular homeostasis and development, is increasingly implicated in cancer biology. Here, we reveal a novel role for TEAD1 in organizing nuclear condensates, independent of active transcription. Using high-resolution imaging, ChIP-seq, RNA-seq and proximity-based proteomics, we demonstrate that in patient-derived renal cell carcinoma cells, TEAD1 forms micron-sized foci by binding to the heterochromatic pericentromeric regions using its DNA-binding domain. These TEAD1 foci do not mediate transcription but instead serve as depots for excess TEAD1. This contrasts with TEAD1 organization in other genomic regions of both RCC and normal kidney cells, where TEAD1 associates with markers of active transcription. Our findings provide a mechanistic framework for TEAD1’s dual regulatory roles, offering new insights into its contribution to transcriptional dysregulation and tumor progression.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Line Cell

DISEASE(S): Renal Cell Carcinoma

SUBMITTER: Danfeng Cai

LAB HEAD: Danfeng Cai

PROVIDER: PXD064255 | Pride | 2025-06-02

REPOSITORIES: Pride

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			Action	DRS
	PeptideGroups.txt	Txt
	ProteinGroups.txt	Txt
	RO_481_CS_241105_CaiD_YW_C5R1.msf	Msf
	RO_481_CS_241105_CaiD_YW_C5R1.mzML	Mzml
	RO_481_CS_241105_CaiD_YW_C5R1.raw	Raw

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TEAD1 condensates are transcriptionally inactive storage sites on the pericentromeric heterochromatin

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