Atypical GATA Transcription Factor TRPS1 Represses Gene Expression by Recruiting CHD4/NuRD(MTA2) and Suppresses Cell Migration and Invasion by Repressing TP63 Expression

Overview

Journal Oncogenesis

Date 2018 Dec 20

PMID 30563971

Citations 16

Authors

Yuzhi Wang

Xue Lin

Xue Gong

Lele Wu

Jun Zhang

Weiguang Liu

Jian Li

Liming Chen

Affiliations

Soon will be listed here.

Abstract

Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1 recognizes both gene proximal and distal transcription start site (TSS) sequences to repress gene expression. Co-IP mass spectrometry and biochemical studies showed that TRPS1 binds to CHD4/NuRD(MTA2). Genome-wide and molecular studies revealed that CHD4/NuRD(MTA2) is required for TRPS1 transcriptional repression. Mechanically, TRPS1 and CHD4/NuRD(MTA2) form precision-guided transcriptional repression machinery in which TRPS1 guides the machinery to specific target sites by recognizing GATA elements, and CHD4/NuRD(MTA2) represses the transcription of target genes. Furthermore, TP63 was identified and validated to be a direct target of TRPS1-CHD4/NuRD(MTA2) complex, which represses TP63 expression by involving decommission of TP63 enhancer in the described precision-guided manner, leading to a reduction of the ΔNp63 level and contributing to migration and invasion of cancer cells.

Citing Articles

TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity.

Tollot-Wegner M, Jessen M, Kim K, Sanz-Moreno A, Spielmann N, Gailus-Durner V Breast Cancer Res. 2024; 26(1):74.

PMID: 38702730 PMC: 11067134. DOI: 10.1186/s13058-024-01824-7.

TRPS1 modulates chromatin accessibility to regulate estrogen receptor alpha (ER) binding and ER target gene expression in luminal breast cancer cells.

Scott T, Sathyan K, Gioeli D, Guertin M PLoS Genet. 2024; 20(2):e1011159.

PMID: 38377146 PMC: 10906895. DOI: 10.1371/journal.pgen.1011159.

TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.

Yang L, Fan Q, Wang J, Yang X, Yuan J, Li Y Cell Death Discov. 2023; 9(1):185.

PMID: 37344459 PMC: 10284899. DOI: 10.1038/s41420-023-01484-0.

Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets.

Singhal P, Veturi Y, Dudek S, Lucas A, Frase A, Van Steen K Am J Hum Genet. 2023; 110(4):575-591.

PMID: 37028392 PMC: 10119154. DOI: 10.1016/j.ajhg.2023.03.007.

TRPS1 Is Differentially Expressed in a Variety of Malignant and Benign Cutaneous Sweat Gland Neoplasms.

Zengin H, Bui C, Rybski K, Pukhalskaya T, Yildiz B, Smoller B Dermatopathology (Basel). 2023; 10(1):75-85.

PMID: 36810569 PMC: 9944056. DOI: 10.3390/dermatopathology10010011.

References

Momeni P, Glockner G, Schmidt O, von Holtum D, Albrecht B, Gillessen-Kaesbach G . Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I. Nat Genet. 1999; 24(1):71-4. DOI: 10.1038/71717. View

Malik T, Shoichet S, Latham P, Kroll T, Peters L, Shivdasani R . Transcriptional repression and developmental functions of the atypical vertebrate GATA protein TRPS1. EMBO J. 2001; 20(7):1715-25. PMC: 145487. DOI: 10.1093/emboj/20.7.1715. View

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

Crooks G, Hon G, Chandonia J, Brenner S . WebLogo: a sequence logo generator. Genome Res. 2004; 14(6):1188-90. PMC: 419797. DOI: 10.1101/gr.849004. View

Radvanyi L, Singh-Sandhu D, Gallichan S, Lovitt C, Pedyczak A, Mallo G . The gene associated with trichorhinophalangeal syndrome in humans is overexpressed in breast cancer. Proc Natl Acad Sci U S A. 2005; 102(31):11005-10. PMC: 1182410. DOI: 10.1073/pnas.0500904102. View

Crook J, Dunn N, Colman A . Repressed by a NuRD. Nat Cell Biol. 2006; 8(3):212-4. DOI: 10.1038/ncb0306-212. View

Stiewe T . The p53 family in differentiation and tumorigenesis. Nat Rev Cancer. 2007; 7(3):165-8. DOI: 10.1038/nrc2072. View

Marfella C, Imbalzano A . The Chd family of chromatin remodelers. Mutat Res. 2007; 618(1-2):30-40. PMC: 1899158. DOI: 10.1016/j.mrfmmm.2006.07.012. View

Lee T, Johnstone S, Young R . Chromatin immunoprecipitation and microarray-based analysis of protein location. Nat Protoc. 2007; 1(2):729-48. PMC: 3004291. DOI: 10.1038/nprot.2006.98. View

10.

Teodoro J, Evans S, Green M . Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. J Mol Med (Berl). 2007; 85(11):1175-86. DOI: 10.1007/s00109-007-0221-2. View

11.

Denslow S, Wade P . The human Mi-2/NuRD complex and gene regulation. Oncogene. 2007; 26(37):5433-8. DOI: 10.1038/sj.onc.1210611. View

12.

Hall J, Georgel P . CHD proteins: a diverse family with strong ties. Biochem Cell Biol. 2007; 85(4):463-76. DOI: 10.1139/O07-063. View

13.

Zhang Y, Liu T, Meyer C, Eeckhoute J, Johnson D, Bernstein B . Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008; 9(9):R137. PMC: 2592715. DOI: 10.1186/gb-2008-9-9-r137. View

14.

Clapier C, Cairns B . The biology of chromatin remodeling complexes. Annu Rev Biochem. 2009; 78:273-304. DOI: 10.1146/annurev.biochem.77.062706.153223. View

15.

Sharov A, Ko M . Exhaustive search for over-represented DNA sequence motifs with CisFinder. DNA Res. 2009; 16(5):261-73. PMC: 2762409. DOI: 10.1093/dnares/dsp014. View

16.

Guo X, Keyes W, Papazoglu C, Zuber J, Li W, Lowe S . TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol. 2009; 11(12):1451-7. PMC: 2920298. DOI: 10.1038/ncb1988. View

17.

Su X, Chakravarti D, Cho M, Liu L, Gi Y, Lin Y . TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature. 2010; 467(7318):986-90. PMC: 3055799. DOI: 10.1038/nature09459. View

18.

Creyghton M, Cheng A, Welstead G, Kooistra T, Carey B, Steine E . Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010; 107(50):21931-6. PMC: 3003124. DOI: 10.1073/pnas.1016071107. View

19.

Yang X, Lu H, Yan B, Romano R, Bian Y, Friedman J . ΔNp63 versatilely regulates a Broad NF-κB gene program and promotes squamous epithelial proliferation, migration, and inflammation. Cancer Res. 2011; 71(10):3688-700. PMC: 3443863. DOI: 10.1158/0008-5472.CAN-10-3445. View

20.

Ramirez J, Dege C, Kutateladze T, Hagman J . MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes. Mol Cell Biol. 2012; 32(24):5078-88. PMC: 3510529. DOI: 10.1128/MCB.00819-12. View