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Global analysis of induced transcription factors and cofactors identifies Tfdp2 as an essential coregulator during terminal erythropoiesis

Authors
  • Chen, Cynthia
  • Lodish, Harvey F.1, 2, 3
  • 1 Whitehead Institute for Biomedical Research
  • 2 and Department of Biology
  • 3 Massachusetts Institute of Technology
Type
Published Article
Journal
Experimental Hematology
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Mar 01, 2014
Identifiers
DOI: 10.1016/j.exphem.2014.03.001
Source
Elsevier
Keywords
License
Unknown

Abstract

Key transcriptional regulators of terminal erythropoiesis, such as GATA1 and TAL1, have been well characterized, but transcription factors and cofactors and their expression modulations have not yet been explored on a global scale. Here we use global gene expression analysis to identify 28 transcription factors and 19 transcriptional cofactors induced during terminal erythroid differentiation and whose promoters are enriched for binding by GATA1 and TAL1. Utilizing protein-protein interaction databases to identify cofactors for each transcription factor, we pinpoint several co-induced pairs, of which E2f2 and its cofactor Tfdp2 were the most highly induced. TFDP2 is a critical cofactor required for proper cell cycle control and gene expression. GATA1 and TAL1 are bound to the regulatory regions of Tfdp2 and upregulate its expression, and knockdown of Tfdp2 results in significantly reduced rates of proliferation, as well as reduced upregulation of many erythroid-important genes. Loss of Tfdp2 also globally inhibits the normal downregulation of many E2F2 target genes, including those that regulate the cell cycle, causing cells to accumulate in S phase and resulting in increased erythrocyte size. Our findings highlight the importance of TFDP2 in coupling the erythroid cell cycle with terminal differentiation and validate this study as a resource for future work on elucidating the role of diverse transcription factors and coregulators in erythropoiesis.

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