Genome-wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators

By M. R. Tijssen, A. Cvejic, Ana Cvejic, A. Joshi, Rebecca Hannah, Rita Ferreira, A. Forrai, Dana C. Bellissimo, S. Oram, P. Smethurst and 8 more. Developmental Cell, 2011

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Summary Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development of individual lineages. Here, we report the genome-wide binding sites for the five key hematopoietic transcription factors—GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL—in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous binding by all five factors was the most enriched pattern and often occurred near known hematopoietic regulators. Eight genes not previously appreciated to function in hematopoiesis that were bound by all five factors were shown to be essential for thrombocyte and/or erythroid development in zebrafish. Moreover, one of these genes encoding the PDZK1IP1 protein shared transcriptional enhancer elements with the blood stem cell regulator TAL1/SCL. Multifactor ChIP-Seq analysis in primary human cells coupled with a high-throughput in vivo perturbation screen therefore offers a powerful strategy to identify essential regulators of complex mammalian differentiation processes.

Subfields: Cell Biology, Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2580dd400a3acd198fe5ad00c53696a14ff596ff

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Citations in the corpus

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia (2012, background): “…-acting regulatory modules (CRM) are occupied by multiple factors (Ghisletti et al. 2010; Lin et al. 2010; Wilson et al. 2010; A He et al. 2011; Q He et al. 2011; Tijssen et al. 2011) and associated with multiple histone modifications (Barski et al. 2007; Mikkelsen et al. 2007; Wang et al. 2008).”
Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing (2015, background): “RUNX1, GATA1, STAT5A and TAL1(SCL) are well-studied transcription factors for their roles in MK differentiation (Crispino, 2005; Olthof et al., 2008; Tijssen et al., 2011).”
Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells (2014, background): “These findings suggested that CSCs are maintained by a microenvironment similar to those of normal stem cells, such as hematopoietic stem cells and neural stem cells (6, 31).”
Transcriptional regulation of macrophage polarization: enabling diversity with identity (2011, background): “Data that have accumulated from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) in recent years indicate that many transcription factors can bind to thousands of sites in the genome, most often concentrated in 'hotspots' that are associated with multiple transcripti”
Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche (2011, background): “HSCs are retained in perivascular niches that are distributed near osteoblasts and within the nonendosteal parenchyma (Kiel et al., 2005; Sugiyama et al., 2006; Lo Celso et al., 2009; Méndez-Ferrer et al., 2010b).”
Latent enhancers activated by stimulation in differentiated cells. (2013, neutral): “Enhancers active in a given tissue are typically co-occupied by multiple TFs enforcing cell-type-specific gene expression programs (Chen et al., 2008; He et al., 2011; Junion et al., 2012; Siersbæk et al., 2011; Song et al., 2011; Tijssen et al., 2011).”