PU.1 and pRB Interact and Cooperate To Repress GATA-1 and Block Erythroid Differentiation
Open accessAbstract
PU.1 and GATA-1 are two hematopoietic specific transcription factors that play key roles in development of the myeloid and erythroid lineages, respectively. The two proteins bind to one another and inhibit each other's function in transcriptional activation and promotion of their respective differentiation programs. This mutual antagonism may be an important aspect of lineage commitment decisions. PU.1 can also act as an oncoprotein since deregulated expression of PU.1 in erythroid precursors causes erythroleukemias in mice. Studies of cultured mouse erythroleukemia cell lines indicate that one aspect of PU.1 function in erythroleukemogenesis is its ability to block erythroid differentiation by repressing GATA-1 (N. Rekhtman, F. Radparvar, T. Evans, and A. I. Skoultchi, Genes Dev. 13:1398-1411, 1999). We have investigated the mechanism of PU.1-mediated repression of GATA-1. We report here that PU.1 binds to GATA-1 on DNA. We localized the repression activity of PU.1 to a small acidic N-terminal domain that interacts with the C pocket of pRB, a well-known transcriptional corepressor. Repression of GATA-1 by PU.1 requires pRB, and pRB colocalizes with PU.1 and GATA-1 at repressed GATA-1 target genes. PU.1 and pRB also cooperate to block erythroid differentiation. Our results suggest that one of the mechanisms by which PU.1 antagonizes GATA-1 is by binding to it at GATA-1 target genes and tethering to these sites a corepressor that blocks transcriptional activity and thereby erythroid differentiation.
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At high levels, PU.1 blocks DNA binding by GATA-1; at lower levels it antagonizes GATA-1-mediated transactivation by forming complexes with it that recruit Rb through the PU.1 acidic transactivation domain.
“At high levels, PU.1 has been found to block DNA binding by GATA-1 (23), while at lower levels it is reported to antagonize GATA-1-mediated transactivation by forming complexes with it that recruit Rb through the PU.1 acidic transactivation domain (101).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [101]
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References 71 · Cited by 102
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- [4]4. Blobel, G. A., T. Nakajima, R. Eckner, M. Montminy, and S. H. Orkin. 1998. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation. Proc. Natl. Acad. Sci. USA 95: 20612066.
- [23]23. Johnson, K. D., J. A. Grass, M. E. Boyer, C. M. Kiekhaefer, G. A. Blobel, M. J. Weiss, and E. H. Bresnick. 2002. Cooperative activities of hematopoietic regulators recruit RNA polymerase II to a tissue-specific chromatin domain. Proc. Natl. Acad. Sci. USA 99: 11760-11765.
- [40]40. Meloni, A. R., E. J. Smith, and J. R. Nevins. 1999. A mechanism for Rb/ p130-mediated transcription repression involving recruitment of the CtBP corepressor. Proc. Natl. Acad. Sci. USA 96: 9574-9579.
- [62]62. Watanabe, G., A. Howe, R. J. Lee, C. Albanese, I. W. Shu, A. N. Karnezis, L. Zon, J. Kyriakis, K. Rundell, and R. G. Pestell. 1996. Induction of cyclin D1 by simian virus 40 small tumor antigen. Proc. Natl. Acad. Sci. USA 93: 1286112866.
- [71]71. Zhang, P., G. Behre, J. Pan, A. Iwama, N. Wara-Aswapati, H. S. Radomska, P. E. Auron, D. G. Tenen, and Z. Sun. 1999. Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc. Natl. Acad. Sci. USA 96: 8705-8710.
- Authors
- Rekhtman, N., Choe, K. S., Matushansky, I., Murray, S., Stopka, T., & Skoultchi, A. I.
- Affiliations
- Albert Einstein College of Medicine (US)
- Department of Cell Biology, Albert Einstein College of Medicine
- Corresponding author
- Skoultchi, Arthur I.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-11
- Volume
- 23
- Issue
- 21
- Pages
- 7460-7474
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC207581
- OpenAlex
- W2159680972
- Cited by
- 102
- References
- 71
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 5
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r37ca016368-24)
- National Cancer Institute (2P30-CA13330, 5R37CA16368, P30CA013330)
- National Institute of General Medical Sciences (5T32GM07288-25, T32GM007288)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- PU.1, retinoblastoma protein, GATA-1, transcriptional repression, erythroid differentiation, erythroleukemia, transcription factor interaction, corepressors, hematopoietic lineage commitment, transcriptional activation
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Binding Sites, Cell Differentiation, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Humans, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Transcription Factors, Transcription, Genetic, Trans-Activators, Erythroid Precursor Cells, Retinoblastoma Protein, Protein Structure, Tertiary, Genes, Reporter, Cell Lineage, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor, Mice
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