Repression by RB1 characterizes genes involved in the penultimate stage of erythroid development

Ji Zhang, Melanie R. Loyd, Mindy S. Randall, John J. Morris, Jayesh G. Shah, Paul A. Ney

Research output: Contribution to journalArticle

Abstract

Retinoblastoma-1 (RB1), and the RB1-related proteins p107 and p130, are key regulators of the cell cycle. Although RB1 is required for normal erythroid development in vitro, it is largely dispensable for erythropoiesis in vivo. The modest phenotype caused by RB1 deficiency in mice raises questions about redundancy within the RB1 family, and the role of RB1 in erythroid differentiation. Here we show that RB1 is the major pocket protein that regulates terminal erythroid differentiation. Erythroid cells lacking all pocket proteins exhibit the same cell cycle defects as those deficient for RB1 alone. RB1 has broad repressive effects on gene transcription in erythroid cells. As a group, RB1-repressed genes are generally well expressed but downregulated at the final stage of erythroid development. Repression correlates with E2F binding, implicating E2Fs in the recruitment of RB1 to repressed genes. Merging differential and time-dependent changes in expression, we define a group of approximately 800 RB1-repressed genes. Bioinformatics analysis shows that this list is enriched for terms related to the cell cycle, but also for terms related to terminal differentiation. Some of these have not been previously linked to RB1. These results expand the range of processes potentially regulated by RB1, and suggest that a principal role of RB1 in development is coordinating the events required for terminal differentiation.

Original languageEnglish (US)
Pages (from-to)3441-3453
Number of pages13
JournalCell Cycle
Volume14
Issue number21
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Retinoblastoma
Genes
Cell Cycle
Erythroid Cells
Proteins
Erythropoiesis
Computational Biology

Keywords

  • Cell cycle
  • Erythroid differentiation
  • Pocket proteins
  • Retinoblastoma-1 protein
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Repression by RB1 characterizes genes involved in the penultimate stage of erythroid development. / Zhang, Ji; Loyd, Melanie R.; Randall, Mindy S.; Morris, John J.; Shah, Jayesh G.; Ney, Paul A.

In: Cell Cycle, Vol. 14, No. 21, 01.01.2015, p. 3441-3453.

Research output: Contribution to journalArticle

Zhang, Ji ; Loyd, Melanie R. ; Randall, Mindy S. ; Morris, John J. ; Shah, Jayesh G. ; Ney, Paul A. / Repression by RB1 characterizes genes involved in the penultimate stage of erythroid development. In: Cell Cycle. 2015 ; Vol. 14, No. 21. pp. 3441-3453.
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