TY - JOUR
T1 - Negative regulation of selected bHLH proteins by eHAND
AU - Bounpheng, Mangkey A.
AU - Morrish, Tammy A.
AU - Dodds, Sherry G.
AU - Christy, Barbara A.
N1 - Funding Information:
We thank Toomas Neuman (Cedars-Sinai Medical Center, Los Angeles, CA), Madis Metsis (Karolinska Institute, Sweden, and Institute of Chemical Physics and Biophysics, Estonia), Stephen Ska-pek (St. Jude’s Childrens Hospital, Memphis, TN), Greg Kato (Johns Hopkins School of Medicine, Baltimore, MD), Stan Hollenberg (Vol-lum Institute, Portland, OR), Barbara Wold (California Institute of Technology, Pasadena, CA), and Meinrad Busslinger (Research Institute of Molecular Pathology, Vienna, Austria) for various plasmid DNA clones and Dr. Eric Olson (UT Southwestern) for the yeast two-hybrid 10.5-day mouse embryo cDNA library. We are grateful to Dr. Anthony Firulli and Dr. Gina Schatteman for the critical reading of the manuscript. This work was supported by Grant 1-FY96-0126 from the March of Dimes Birth Defects Foundation and by Grant 98G-345 from the American Heart Association, Texas Affiliate.
PY - 2000/6/15
Y1 - 2000/6/15
N2 - The bHLH protein eHAND plays an important role in the development of extraembryonic, mesodermal, and cardiac cell lineages, presumably through heterodimerization with other HLH proteins and DNA binding. In this study, we have identified a novel transcriptional activity of eHAND. In transient transfection assays, eHAND is a potent inhibitor of activation by some but not all bHLH proteins, eHAND can prevent E-box DNA binding by these bHLH proteins. Interestingly, eHAND can also strongly inhibit transactivation activity by a MyoD~E47 tethered dimer, which suggests a distinct mechanism of action. eHAND also inhibits MyoD-dependent skeletal muscle cell differentiation and expression of the muscle-specific myosin heavy chain protein. In addition, we show that eHAND can repress activity of the natural p75LNGFR promoter, whose expression overlaps that of eHAND and dHAND. The inhibitory activity of eHAND may be attributed to multiple mechanisms, such as the ability to act as a corepressor, the presence of a repression domain, and its ability to sequester E proteins in an inactive complex. Based upon its inhibitory effect on bHLH proteins and cellular differentiation, we propose that eHAND may function by several mechanisms to promote placental giant cell proliferation by negatively regulating the activities of the bHLH protein MASH-2. (C) 2000 Academic Press.
AB - The bHLH protein eHAND plays an important role in the development of extraembryonic, mesodermal, and cardiac cell lineages, presumably through heterodimerization with other HLH proteins and DNA binding. In this study, we have identified a novel transcriptional activity of eHAND. In transient transfection assays, eHAND is a potent inhibitor of activation by some but not all bHLH proteins, eHAND can prevent E-box DNA binding by these bHLH proteins. Interestingly, eHAND can also strongly inhibit transactivation activity by a MyoD~E47 tethered dimer, which suggests a distinct mechanism of action. eHAND also inhibits MyoD-dependent skeletal muscle cell differentiation and expression of the muscle-specific myosin heavy chain protein. In addition, we show that eHAND can repress activity of the natural p75LNGFR promoter, whose expression overlaps that of eHAND and dHAND. The inhibitory activity of eHAND may be attributed to multiple mechanisms, such as the ability to act as a corepressor, the presence of a repression domain, and its ability to sequester E proteins in an inactive complex. Based upon its inhibitory effect on bHLH proteins and cellular differentiation, we propose that eHAND may function by several mechanisms to promote placental giant cell proliferation by negatively regulating the activities of the bHLH protein MASH-2. (C) 2000 Academic Press.
KW - Differentiation
KW - Transcriptional repression
KW - bHLH proteins
KW - eHAND
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U2 - 10.1006/excr.2000.4898
DO - 10.1006/excr.2000.4898
M3 - Article
C2 - 10837146
AN - SCOPUS:0034659846
VL - 257
SP - 320
EP - 331
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 2
ER -