Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 444, Issue 4, Pages 634-637Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.01.143
Keywords
PITX2; MLL4/KMT2D; PTIP; Histone H3 lysine 4 (H3K4); Histone lysine methyltransferase (HKMT)
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Funding
- U.S. National Science Foundation [EPS-1003907]
- West Virginia state Research Challenge Fund
- Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [R15HD062979, R03HD071116]
- Office Of The Director
- Office of Integrative Activities [1003907] Funding Source: National Science Foundation
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Pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of Wnt/beta-catenin signaling, plays substantial roles in embryonic development and human disorders. The mechanism of its functions, however, is not fully understood. In this study, we demonstrated that PITX2 associated with histone H3 lysine 4 (H3K4) methyltransferase (HKMT) mixed-lineage leukemia 4 (MLL4/KMT2D), Pax transactivation domain-interacting protein (PTIP), and other H3K4.HKMT core subunits. This association of PITX2 with H3K4-HKMT complex was dependent on PITX2's homeodomain. Consistently, the PITX2 protein complex was shown to possess H3K4.HKMT activity. Furthermore, the chromatin immunoprecipitation result revealed co-occupancy of PITX2 and PTIP on the promoter of the PITX2's transcriptional target. Taken together, our data provide new mechanistic perspectives on PITX2's functions and its related biological processes. (C) 2014 Elsevier Inc. All rights reserved.
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