Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 320-331 |
| Number of pages | 12 |
| Journal | Experimental Cell Research |
| Volume | 257 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 15 2000 |
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Keywords
- bHLH proteins
- Differentiation
- eHAND
- Transcriptional repression
ASJC Scopus subject areas
- Cell Biology
Cite this
Negative regulation of selected bHLH proteins by eHAND. / Bounpheng, Mangkey A.; Morrish, Tammy A.; Dodds, Sherry G.; Christy, Barbara A.
In: Experimental Cell Research, Vol. 257, No. 2, 15.06.2000, p. 320-331.Research output: Contribution to journal › Article
}
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.
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 - bHLH proteins
KW - Differentiation
KW - eHAND
KW - Transcriptional repression
UR - http://www.scopus.com/inward/record.url?scp=0034659846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034659846&partnerID=8YFLogxK
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 -