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. 2018 Apr 9;128(5):1937–1955. doi: 10.1172/JCI95089

Figure 13. A proposed model of ZMYND8 in regulation of HIF transcriptional activity and breast cancer progression and metastasis.

Figure 13

ZMYND8 is localized at the HREs through H3K14ac and H4K16ac and acetylated at lysines 1007 and 1034 by p300 in breast cancer cells. Acetylated ZMYND8 recruits BRD4 to the HREs to form a HIF transactivation complex. Upon HIF binding to the HRE under hypoxia, ZMYND8/BRD4 are further enriched at the HREs and enhance RNA polymerase II phosphorylation at serine 2 and subsequent transcriptional elongation of the HIF target genes in breast cancer cells, thereby increasing angiogenesis and cell motility and decreasing cell death to promote breast cancer progression and metastasis. ZMYND8 itself is induced by HIF-1 and HIF-2 and thus amplifies HIF activity and HIF-mediated breast cancer progression and metastasis.