Author:
Robertson Anthony J,Dickey-Sims Carrie,Ransick Andrew,Rupp Dawn E,McCarthy John J,Coffman James A
Abstract
Abstract
Background
Runx proteins are developmentally important metazoan transcription factors that form a heterodimeric complex with the non-homologous protein Core Binding Factor β (CBFβ). CBFβ allosterically enhances Runx DNA binding but does not bind DNA itself. We report the initial characterization of SpCBFβ, the heterodimeric partner of SpRunt-1 from the sea urchin Stronylocentrotus purpuratus.
Results
SpCBFβ is remarkably similar to its mammalian homologues, and like them it enhances the DNA binding of the Runt domain. SpCBFβ is entirely of zygotic provenance and its expression is similar that of SpRunt-1, accumulating globally at late blastula stage then later localizing to endoderm and oral ectoderm. Unlike SpRunt-1, however, SpCBFβ is enriched in the endodermal mid- and hindgut of the pluteus larva, and is not highly expressed in the foregut and ciliated band. We showed previously that morpholino antisense-mediated knockdown of SpRunt-1 leads to differentiation defects, as well as to extensive post-blastula stage apoptosis caused by under-expression of the Runx target gene SpPKC1. In contrast, we show here that knockdown of SpCBFβ does not negatively impact cell survival or SpPKC1 expression, although it does lead to differentiation defects similar to those associated with SpRunt-1 deficiency. Moreover, SpRunt-1 containing a single amino acid substitution that abolishes its ability to interact with SpCBFβ retains the ability to rescue cell survival in SpRunt-1 morphant embryos. Chromatin immunoprecipitation shows that while the CyIIIa promoter engages both proteins, the SpPKC1 promoter only engages SpRunt-1.
Conclusion
SpCBFβ is a facultative Runx partner that appears to be required specifically for cell differentiation.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Developmental Biology,Plant Science,General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Physiology,Ecology, Evolution, Behavior and Systematics,Structural Biology,Biotechnology
Reference26 articles.
1. Coffman JA: Runx transcription factors and the developmental balance between cell proliferation and differentiation. Cell Biol Int. 2003, 27 (4): 315-324. 10.1016/S1065-6995(03)00018-0.
2. Kagoshima H, Shigesada K, Satake M, Ito Y, Miyoshi H, Ohki M, Pepling M, Gergen P: The Runt domain identifies a new family of heteromeric transcriptional regulators. Trends Genet. 1993, 9 (10): 338-341. 10.1016/0168-9525(93)90026-E.
3. Rennert J, Coffman JA, Mushegian AR, Robertson AJ: The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms. BMC Evol Biol. 2003, 3: 4-10.1186/1471-2148-3-4.
4. Coffman JA, Moore JG, Calzone FJ, Britten RJ, Hood LE, Davidson EH: Automated sequential affinity chromatography of sea urchin embryo DNA binding proteins. Mol Mar Biol Biotechnol. 1992, 1 (2): 136-146.
5. Coffman JA, Kirchhamer CV, Harrington MG, Davidson EH: SpRunt-1, a new member of the runt domain family of transcription factors, is a positive regulator of the aboral ectoderm-specific CyIIIA gene in sea urchin embryos. Dev Biol. 1996, 174 (1): 43-54. 10.1006/dbio.1996.0050.
Cited by
14 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献