Research Papers:

SUMOylation of HP1α supports association with ncRNA to define responsiveness of breast cancer cells to chemotherapy

Feng-Ming Lin, Santosh Kumar, Jing Ren, Samaneh Karami, Shaymaa Bahnassy, Yue Li, Xiaofeng Zheng, Jing Wang and Tasneem Bawa-Khalfe _

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Oncotarget. 2016; 7:30336-30349. https://doi.org/10.18632/oncotarget.8733

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Feng-Ming Lin1, Santosh Kumar2, Jing Ren2, Samaneh Karami2, Shaymaa Bahnassy2, Yue Li3, Xiaofeng Zheng4, Jing Wang4 and Tasneem Bawa-Khalfe2

1 Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2 Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA

3 Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX, USA

4 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Tasneem Bawa-Khalfe, email:

Keywords: SUMO, SENP7, HP1α, ncRNA, Rad51C

Received: March 31, 2016 Accepted: April 03, 2016 Published: April 14, 2016


Epigenetic reprogramming allows cancer cells to bypass normal checkpoints and potentiate aberrant proliferation. Several chromatin regulators are subject to reversible SUMO-modification but little is known about how SUMOylation of chromatin-remodelers modulates the cancer epigenome. Recently, we demonstrated that SUMO-protease SENP7L is upregulated in aggressive BCa and maintains hypoSUMOylated heterochromatin protein 1-α (HP1α). Canonical models define HP1α as a “reader” of repressive H3K9m3 marks that supports constitutive heterochromatin. It is unclear how SUMOylation affects HP1α function in BCa cells. This report shows HP1α SUMO-dynamics are closely regulated in a complex with SENP7L and SUMO-E3 Polycomb-2 (PC2/CBX4). This complex accumulates at H3K9m3 sites, hypoSUMOylates HP1α and PC2, and reduces PC2’s SUMO-E3 activity. HyperSUMO conditions cause complex dissociation, SUMOylation of PC2 and HP1α, and recruitment of SUMOylated HP1α to multiple DNA-repair genes including Rad51C. SUMOylated HP1α’s enrichment at euchromatin requires chromatin-bound non-coding RNA (ncRNA), reduces Rad51C protein, and increases DNA-breaks in BCa cells. Hence, HP1α SUMOylation and consistently low SENP7L increase efficacy of DNA-damaging chemotherapeutic agents. BCa patients on chemotherapy that express low SENP7L exhibit greater survival rates than patients with high SENP7L. Collectively, these studies suggest that SUMOylated HP1α is a critical epigenetic-regulator of DNA-repair in BCa that could define chemotherapy responsiveness.

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