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GATA3 cooperates with PARP1 to regulate CCND1 transcription through modulating histone H1 incorporation

Oncogene volume 33, pages 3205–3216 (2014)Cite this article

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Abstract

The transcription factor GATA3 is a key regulator of mammary gland development and a definitive marker of luminal breast cancer. However, the molecular mechanisms underlying the role of GATA3 in breast carcinogenesis is still not fully understood. We report here that GATA3 promotes cell proliferation and tumorigenesis by facilitating the G1/S transition through its transcription regulation of the CCND1 gene in breast cancer cells. We found that GATA3 is physically associated with poly-ADP ribose polymerase-1 (PARP1), an enzyme modifying nuclear proteins by poly(ADP-ribosyl)ation. We showed that PARP1 acts as a transcription coactivator for GATA3 in breast cancer cells and demonstrated that GATA3 cooperates with PARP1 in transactivation of the CCND1 gene. We demonstrated that PARP1 competes with linker histone H1 to maintain a transcriptional competent chromatin environment for CCND1 gene. Our results unveiled a molecular basis for the coordinated regulation between GATA3 and PARP1 in transcription activation, providing a mechanism for GATA3 in breast carcinogenesis.

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Acknowledgements

This work was supported by grants (81130048 to YS, 81272284 and 91219102 to Lei Shi) from the National Natural Science Foundation of China and grants (973 Program: 2011CB504204 to YS) from the Ministry of Science and Technology of China.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China

    L Shan, X Li, L Liu, Q Wang, Y Zheng, Y Duan, C Xuan, Y Wang, Y Shang & L Shi

  2. Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    X Ding & F Yang

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Shan, L., Li, X., Liu, L. et al. GATA3 cooperates with PARP1 to regulate CCND1 transcription through modulating histone H1 incorporation. Oncogene 33, 3205–3216 (2014). https://doi.org/10.1038/onc.2013.270

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