295 research outputs found
Supplementary_Table_S1_ – Supplemental material for Rewiring of the Transcription Factor Network in Acute Myeloid Leukemia
No full textSupplemental material, Supplementary_Table_S1_ for Rewiring of the Transcription Factor Network in Acute Myeloid Leukemia by Salam A Assi, Constanze Bonifer and Peter N Cockerill in Cancer Informatics</p
Developmental changes in the differentiation capacity of hematopoietic stem cells
No full textHaematopoietic stem cells (HSCs) can be found in different locations of the developing vertebrate organism. Recent studies have detected functional changes in the haematopoietic system during ontogeny. Depending on the developmental stage, HSCs create different progeny, which express distinct marker genes. In addition, haematopoietic development is differentially affected by a variety of mutations. Here, Constanze Bonifer and colleagues discuss the existence of HSCs with specific differentiation capacities.<br/
What Can We Learn from Flies: Epigenetic Mechanisms Regulating Blood Cell Development in Drosophila:Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development
No full textDrosophila (fruit flies) possess a highly effective innate immune system that provides defence against pathogens that include bacteria, fungi and parasites. Pathogens are neutralised by mechanisms that include phagocytosis, encapsulation and melanisation. Circulating cells called haemocytes are a key component of the innate immune system and include cells that resemble the granulocyte–macrophage lineages of mammals. The mechanisms that regulate Drosophila haematopoietic progenitor specification and differentiation are highly conserved, allowing Drosophila to be used as a useful model to understand transcriptional regulation of haematopoiesis. In this review I will summarise the mesodermal origin of Drosophila haemocyte precursors and describe parallels with mammalian haemangioblast precursors. I will discuss key signalling pathways and transcription factors that regulate differentiation of the three principal haemocyte cell types. There are significant parallels with the transcriptional circuitry that controls mammalian haematopoiesis, with transcription factors such as GATA factors, RUNX family members and STAT proteins influencing the specification and differentiation of Drosophila haemocytes. These transcription factors recruit co-repressor or co-activator complexes that alter chromatin structure to regulate gene expression. I will discuss how the Drosophila haematopoietic compartment has been used to explore function of ATP-dependent chromatin remodelling complexes and histone modifying complexes. As key regulators of haematopoiesis are conserved, the great genetic amenability of Drosophila offers a powerful system to dissect function of leukaemogenic fusion proteins such as RUNX1-ETO. In the final section of the review the use of genetic screens to identify novel RUNX1-ETO interacting factors will be discussed
Long range chromatin mechanisms regulating gene locus activation
No full textSeveral different types of regulatory mechanisms contribute to the tissue- and development-specific regulation of a gene. It is now well established that, in addition to promoters, upstream cis-regulatory elements, which bind a variety of trans-acting factors, are essential for correct gene activation. In the last few years, however, it has become evident that the chromatin structure of eukaryotic genes is an important additional regulatory layer that is essential for correct gene expression during development. Chromatin is essentially a repressive environment for transcription factors; hence, much effort in recent years has been devoted to the elucidation of how these repressive forces are overcome during the process of gene locus activation. A particular interesting question in this context is: what are the molecular mechanisms by which extensive regions of chromatin, in many cases far outside the coding region, are reorganized during development? In this review, I summarize data from recent investigations that have uncovered a surprising variety of factors involved in this process
Tagging methods as a tool to investigate histone H3 methylation dynamics in mouse embryonic stem cells
Get PDFCovalent modification of histones is an important factor in the regulation of the chromatin structure implicated in DNA replication, repair, recombination, and transcription, as well as in RNA processing. In recent years, histone methylation has emerged as one of the key modifications regulating chromatin function. However, the mechanisms involved are complex and not well understood. Histone 3 lysine 4 (H3K4) methylation is deposited by a family of histone H3K4 methyltransferases (HMTs) that share a conserved SET domain. In mammalian cells, six family members have been characterized: Setd1a and Setd1b (the mammalian orthologs of yeast Set1) and four Mixed lineage leukemia (Mll) family HMTs, which share limited similarity with yeast Set1 beyond the SET domain. Several studies demonstrated that the H3K4 methyltransferases exist as multiprotein complexes. To functionally dissect H3K4 methyltransferase complexes, GFP tagging of the core subunit Ash2l and the complex-specific subunits Cxxc1 and Wdr82 (Setd1a/b complexes) Men1 (Mll1/2 complexes), and Ptip (Mll3/Mll4 complexes), was used. The fusion proteins were successfully expressed in mouse embryonic stem cells (ES cells), analyzed by confocal microscopy, Mass Spectrometry (MS) and ChIP-seq. Ptip was the only subunit able to bind mitotic chromatin. Additionally, both Ptip and Wdr82 were found to associate with cell cycle regulators, suggesting a possible role of the two proteins or respective complexes in cell cycle regulation.
Mass Spectrometry revealed that Wdr82 and Ptip interact with members of he PAF complex, and ChIP-seq showed that Wdr82, Cxxc1 and Ptip positively modulate pluripotency genes. Thus, Setd1a/b and Mll3/4 complexes might act together in the regulation of embryonic stem cells identity. Protein pull downs identified at least one new Setd1a/b interactor, Bod1l that is orthologous to the yeast protein Sgh1, a component of the Set1C complex. Furthermore, our MS and ChIP-seq data suggested that only Mll2 complex binds to bivalent promoters, wheras Mll2 and Setd1a complexes might function together in a set of promoters
Endothélium hémogénique et production des cellules souches hématopoïétiques / Hemogenic Endothelium and Hematopoietic Stem Cell Production
No full textSéminaire organisé par Thierry Jaffredo (CNRS-UPMC UMR7622, InsermU115, Paris, France), Georges Lacaud (Cancer Research UK Manchester Institute, UK) et Catherine Robin (Hubrecht Institute, Utrecht, Pays-Bas) du 20 au 25 mars 2017 Participants Anna Bigas, Constanze Bonifer, Marella de Bruijn, Andrea Ditadi, Charles Durand, Andrew Elefanty, Thierry Jaffredo, Valérie Kouskoff, Georges Lacaud, Alexander Medvinsky, Pablo Menendez, Elizabeth Ng, Trista North, James Palis, Roger Patient, Catherine R..
Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development. Epigenetics and Human Health
No full textTranscriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development. Epigenetics and Human Health
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