Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation

By Kairong Cui, Chongzhi Zang, Tae-Young Roh, Dustin E. Schones, R. Childs, Weiqun Peng, Keji Zhao. Cell Stem Cell, 2009

644 citations recorded by the source corpus.

Summary Histone modifications have been implicated in stem cell maintenance and differentiation. We have analyzed genome-wide changes in gene expression and histone modifications during differentiation of multipotent human primary hematopoietic stem/progenitor cells (HSCs/HPCs) into erythrocyte precursors. Our data indicate that H3K4me1, H3K9me1 and H3K27me1 associate with enhancers of differentiation genes prior to their activation and correlate with basal expression, suggesting that these mono-methylations are involved in the maintenance of activation potential required for differentiation. In addition, although the majority of genes associated with both H3K4me3 and H3K27me3 in HSCs/HPCs become silent and lose H3K4me3 after differentiation, those that lose H3K27me3 and become activated after differentiation are associated with increased levels of H2A.Z, H3K4me1, H3K9me1, H4K20me1 and RNA polymerase II in HSCs/HPCs. Thus, our results suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and we provide a resource for enhancer and promoter identification.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2d40982c3bc99b14d5117ec0bb6d22adbfaf2511

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

Enhancer function: new insights into the regulation of tissue-specific gene expression (2011, positive): “Interestingly, some of these histone modifications may serve as marks for future gene expressio”
Transcriptional regulation by Polycomb group proteins (2013, background): “; and from the Novo Nordisk Foundation, the Danish Cancer Society and the Danish Council for Strategic Research (12-110503) to K.”
Aberrant epigenetic landscape in cancer: how cellular identity goes awry. (2010, background): “, 2007) in more lineage-restricted but nonetheless multipotent progenitors (Cui et al., 2009; Orford et al., 2008) and in terminally differentiated cells that can be reprogrammed in the presence of external stimuli (Roh et al.”
Modeling gene expression using chromatin features in various cellular contexts (2012, neutral): “Several early studies [7,32-38] either simply described this relationship or quantified chromatin features and/or expression.”
Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders (2010, background): “In hemopoietic stem cells, many genes involved in cell fate decisions are held in a transcriptionally poised 'bivalent' state characterized by both active (H3K4me2 and H3K4me3) and repressive (H3K27me3) histone mark”
Distinct DNA methylomes of newborns and centenarians (2012, background): “0029) (39), as has recently been suggested (33–36).”
A decade of exploring the cancer epigenome — biological and translational implications (2011, methodology): “Next-generation sequencing techniques, as applied to mapping chromatin and DNA methylation in normal, cancer and induced pluripotent stem cells (iPSs), have revolutionized our knowledge of chromatin states, nucleosome positioning and how alterations in these contribute to diseas”
The Polycomb Complex PRC2 and its Mark in Life (2011, background): “The monomethylated version of H3K27 is associated with constitutive heterochromatin — a more stably silent, gene-poor region of chromatin — but its enrichment through the gene body is correlated with actively transcribed gene”
Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage (2012, neutral): “Modifications included H3K27me3 and H3K4me3 (associated with inactive and active promoters respectively) and H3K4me1 and H3K27ac (associated with promoters and enhancers) (Barski et al., 2007; Cui et al., 2009; Ernst et al., 2011; Mikkelsen et al., 2007; Zhou et al., 2011).”
A double take on bivalent promoters. (2013, background): “Moreover, multipotent human hematopoietic stem cells contain ;3000 bivalently marked promoters (Cui et al. 2009).”
Histone H3K27ac separates active from poised enhancers and predicts developmental state (2010, background): “Furthermore, large sets of inactive developmental genes in hematopoietic stem cells are associated with H3K4me1-enriched distal enhancers (13).”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “Similar patterns are also evident along the axis of haematopoietic differentiation, as indicated by the analysis of in vivo lineages from both human and mous”
A clustering approach for identification of enriched domains from histone modification ChIP-Seq data (2009, methodology): “CD133+ and CD36+ cells were obtained from Cui et al. (2009). The histone modification data for mouse Th1, Th2 and Th17 CD4+ T-cells were obtained from Wei et al. (2009). The IgG control library for the human resting CD4+ T-cells and ‘input’ control libraries for the human CD133+ and CD36+ cells are ”
Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities (2010, methodology): “, 2007), and CD36 erythrocyte precursors (Cui et al., 2009).”
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression (2009, background): “To further extend the catalog of lincRNAs, we sought to analyze chromatin-state maps of 6 human cell types: hESC (10), 2 hematopoietic stem cells (CD133 and CD36 ) (15), T-cells (6), hLFs (1), and normal embryonic kidney (hEK).”