scholarly journals Constraint of gene expression by the chromatin remodelling protein CHD4 facilitates lineage specification

Development ◽  
2015 ◽  
Vol 142 (15) ◽  
pp. 2586-2597 ◽  
Author(s):  
Aoife O'Shaughnessy-Kirwan ◽  
Jason Signolet ◽  
Ita Costello ◽  
Sarah Gharbi ◽  
Brian Hendrich
Keyword(s):  
Gene Expression ◽  
Chromatin Remodelling ◽  
Lineage Specification

Epigenetic control of cellular senescence in disease: opportunities for therapeutic intervention

2007 ◽  
Vol 9 (7) ◽  
pp. 1-26 ◽  
Author(s):  
Stuart P. Atkinson ◽  
W. Nicol Keith
Keyword(s):  
Gene Expression ◽  
Cellular Senescence ◽  
Chromatin Remodelling ◽  
Telomere Maintenance ◽  
Cell Physiology ◽  
Gene Promoters ◽  
Epigenetic Mechanisms ◽  
Histone Proteins ◽  
Regulate Gene Expression ◽  
Regulate Gene

AbstractUnderstanding how senescence is established and maintained is an important area of study both for normal cell physiology and in tumourigenesis. Modifications to N-terminal tails of histone proteins, which can lead to chromatin remodelling, appear to be key to the regulation of the senescence phenotype. Epigenetic mechanisms such as modification of histone proteins have been shown to be sufficient to regulate gene expression levels and specific gene promoters can become epigenetically altered at senescence. This suggests that epigenetic mechanisms are important in senescence and further suggests epigenetic deregulation could play an important role in the bypass of senescence and the acquisition of a tumourigenic phenotype. Tumour suppressor proteins and cellular senescence are intimately linked and such proteins are now known to regulate gene expression through chromatin remodelling, again suggesting a link between chromatin modification and cellular senescence. Telomere dynamics and the expression of the telomerase genes are also both implicitly linked to senescence and tumourigenesis, and epigenetic deregulation of the telomerase gene promoters has been identified as a possible mechanism for the activation of telomere maintenance mechanisms in cancer. Recent studies have also suggested that epigenetic deregulation in stem cells could play an important role in carcinogenesis, and new models have been suggested for the attainment of tumourigenesis and bypass of senescence. Overall, proper regulation of the chromatin environment is suggested to have an important role in the senescence pathway, such that its deregulation could lead to tumourigenesis.

scholarly journals Gastrointestinal transcription factors drive lineage-specific developmental programs in organ specification and cancer

2019 ◽  
Vol 5 (12) ◽  
pp. eaax8898 ◽  
Author(s):  
Roshane Francis ◽  
Haiyang Guo ◽  
Catherine Streutker ◽  
Musaddeque Ahmed ◽  
Theodora Yung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Epigenetic Regulation ◽  
Gastrointestinal Cancer ◽  
Chromatin Accessibility ◽  
Lineage Specification ◽  
Developmental Programs ◽  
Tissue Specific ◽  
Cancer Data ◽  
Gastrointestinal Tissue

Transcription factors (TFs) are spatially and temporally regulated during gut organ specification. Although accumulating evidence shows aberrant reactivation of developmental programs in cancer, little is known about how TFs drive lineage specification in development and cancer. We first defined gastrointestinal tissue–specific chromatin accessibility and gene expression during development, identifying the dynamic epigenetic regulation of SOX family of TFs. We revealed that Sox2 is not only essential for gastric specification, by maintaining chromatin accessibility at forestomach lineage loci, but also sufficient to promote forestomach/esophageal transformation upon Cdx2 deletion. By comparing our gastrointestinal lineage-specific transcriptome to human gastrointestinal cancer data, we found that stomach and intestinal lineage-specific programs are reactivated in Sox2high/Sox9high and Cdx2high cancers, respectively. By analyzing mice deleted for both Sox2 and Sox9, we revealed their potentially redundant roles in both gastric development and cancer, highlighting the importance of developmental lineage programs reactivated by gastrointestinal TFs in cancer.

scholarly journals Bovine lineage specification revealed by single-cell gene expression analysis from zygote to blastocyst†

2017 ◽  
Vol 97 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Qingqing Wei ◽  
Liang Zhong ◽  
Shaopeng Zhang ◽  
Haiyuan Mu ◽  
Jinzhu Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Lineage Specification ◽  
Cell Gene Expression ◽  
Cell Gene

The Potent Deacetylase Inhibitor Trichostatin a (TSA) Increases CXCR4 Expression in Hematopoietic Stem/Progenitor Cells by Chromatin Remodelling

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3487-3487 ◽  
Author(s):  
Hilal Gul ◽  
Leah A. Marquez-Curtis ◽  
Jennifer Lo ◽  
Nadia Jahroudi ◽  
A. Robert Turner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Trichostatin A ◽  
Mrna Level ◽  
Hdac Inhibitors ◽  
Cxcr4 Expression ◽  
Chromatin Remodelling ◽  
Hematopoietic Stem ◽  
Chip Analysis

Abstract Stromal-cell derived factor (SDF)-1α/CXCL12 and its cognate receptor, CXCR4, play a crucial role in the trafficking of normal hematopoietic stem/progenitor cells (HSPC) and their homing/retention in bone marrow. Consequently, modulation of CXCR4 expression in HSPC could be applied therapeutically to improve the efficiency of HSPC transplantation. It is known that gene expression can be regulated by chromatin remodelling. Two groups of histone modifying enzymes, histone acetyltransferase (HAT) and histone deacetylase (HDAC) participate in the regulation of chromatin structure, and hence gene expression. Disruption of normal HAT or HDAC activities has been found in many human cancers. Recently, several structurally diverse and highly specific HDAC inhibitors (HDI) have been reported. They act as strong modulators of growth, differentiation and apoptosis in several types of cancer, particularly acute myeloid leukemia (AML). However, very little is known regarding the effects of HDI on HSPC. We have previously shown that a specific short-chain fatty acid HDI, valproic acid (VPA), enhances CXCR4 expression and function in normal HSPC (Blood2007: 110; 425a). In order to determine whether other structurally diverse classes of HDI are able to influence CXCR4 expression in HSPC through chromatin remodelling, we investigated the effect of potent hydroxamic acid HDI Trichostatin A (TSA) on CXCR4 in normal HSPC. We examined the effect of TSA on CXCR4 expression (by FACS and real-time RT-PCR), modulation of CXCR4 transcription (chromatin immunoprecipitation (X-ChIP) analysis) and on functional response towards an SDF-1α gradient (by chemotaxis assay) of HSPC (CD34+ cells from cord blood (CB) and the models of immature hematopoietic cells expressing CD34 antigen, namely AML cell lines KG-1a and KG-1). Cells were incubated for 24 h in IMDM supplemented with 20% FCS in the presence of TSA (0.1 μM). We found that TSA increases the percentage of CXCR4-expressing CB CD34+, KG-1a, KG-1 cells (2.5-, 8- and 3-fold, respectively). This effect was also confirmed at the mRNA level in CB CD34+, KG-1a and KG-1 cells (by about 2.5-, 5- and 2.5-fold up-regulation, respectively). Moreover, X-ChIP analysis showed a significant increase in association of acetyl-histone H4 binding to the CXCR4 promoter in CB CD34+ and KG-1 cells (2- and 1.7-fold, respectively). TSA was also shown to significantly increase the chemotaxis of KG-1a cells towards SDF-1α (20 ng/mL), which was inhibited by AMD3100, a potent antagonist of CXCR4. We conclude that other HDI such as TSA regulate CXCR4 expression in HSPC by chromatin remodelling and we suggest that priming of HSPC with HDI may improve their homing and engraftment into bone marrow, especially in CB transplantation.

The Ordered Expression of Transcription Factors Directs Hierarchical Lineage Specification of Eosinophils, Basophils and Mast Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 224-224
Author(s):  
Hiromi Iwasaki ◽  
Yojiro Arinobu ◽  
Shin-ichi Mizuno ◽  
Hirokazu Shigematsu ◽  
Kiyoshi Takatsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Mast Cell ◽  
Cell Fate ◽  
Gene Expression Analysis ◽  
Lineage Specification ◽  
Retroviral Transduction ◽  
Cell Lineages ◽  
Stem And Progenitor Cells ◽  
Eosinophil Colonies

Abstract Here we show that eosinophil progenitors (EoPs) and basophil/mast cell progenitors (BMCPs) are prospectively isolatable in normal hematopoiesis, and that their lineage decisions are regulated principally by GATA-2 and C/EBPα. These progenitors were isolated downstream of granulocyte/monocyte progenitors (GMPs), and BMCPs further generated monopotent basophil progenitors (BaPs) and mast cell progenitors (MCPs). Gene expression analysis showed that neither GATA-1 nor GATA-2 was expressed in GMPs, whereas both of them were upregulated in EoPs, BMCPs, BaPs and MCPs. Importantly, C/EBPα was expressed in EoPs and BaPs as well as GMPs, but was downregulated in BMCPs and MCPs. We have reported that GATA-1 is critical primarily for megakaryocyte/erythrocyte commitment or conversion of stem and progenitor cells. We therefore focused on GATA-2 and C/EBPα functions in this study. Since both EoPs and BaPs co-expressed GATA-2 and C/EBPα while GMPs expressed only C/EBPα, we first transduced GATA-2 into GMPs via a GFP-tagged retrovirus. Strikingly, all GATA-2+ GMPs gave rise to pure eosinophil colonies but not basophil colonies, indicating that enforced GATA-2 can instruct GMPs to become EoPs. Next, since BMCPs only expressed GATA-2 but not C/EBPα, we maintained the expression of C/EBPα in GMPs by retroviral transduction. Interestingly, the sustained expression of C/EBPα blocked basophil/mast cell differentiation from GMPs, indicating that C/EBPα downregulation is required for GMPs to choose the basophil/mast cell fate. As a reciprocal experiment, we conditionally disrupted C/EBPα gene at the level of GMPs by retrovirally transducing Cre gene into GMPs purified from mice in which C/EBPα gene is flanked by loxP sequences (floxed: F). The frequency of mast cell read-out from C/EBPα-disrupted GMPs was 5-fold higher than that from C/EBPα F/F (Cre−) GMPs. C/EBPα-disrupted GMPs, however, did not give rise to BaPs. Furthermore, MCPs transduced with C/EBPα were converted into BaPs. Thus, C/EBPα is required to be reactivated during transition from BMCPs to BaPs. We further tested their interplay in specification of these lineages by using common lymphoid progenitors (CLPs), which do not express GATA-2 or C/EBPα. We enforced the expression of each transcription factor in CLPs in different orders by using the two-step retroviral transduction system. Interestingly, C/EBPα transduction reprogrammed CLPs into GM lineages, and subsequently-transduced GATA-2 instructed C/EBPα + CLPs to select the eosinophil fate. Next, we switched the order of transduction. Strikingly, GATA-2 transduction converted CLPs into BMCPs, and subsequently-transduced C/EBPα specified GATA-2+ CLPs to become BaPs. Thus, at the branchpoint for EoPs and BMCPs, GATA-2 upregulation instructed EoP development if C/EBPα was present, whereas it instructed BMCP development if C/EBPα was absent. After the BMCP stage, C/EBPα had to remain suppressed for MCP development, whereas BaPs developed by C/EBPα reactivation. These data collectively suggest that the order of expression of GATA-2 and C/EBPα is critical for their interplay to selectively activate developmental programs for the eosinophil, the basophil and the mast cell lineages.

scholarly journals The BAF chromatin remodelling complex is an epigenetic regulator of lineage specification in the early mouse embryo

Development ◽  
2016 ◽  
Vol 143 (8) ◽  
pp. 1271-1283 ◽  
Author(s):  
Maryna Panamarova ◽  
Andy Cox ◽  
Krzysztof B. Wicher ◽  
Richard Butler ◽  
Natalia Bulgakova ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Chromatin Remodelling ◽  
Lineage Specification ◽  
Chromatin Remodelling Complex ◽  
Early Mouse Embryo ◽  
Epigenetic Regulator ◽  
Early Mouse

scholarly journals GATA-1 Dominantly Activates a Program of Erythroid Gene Expression in Factor-Dependent Myeloid FDCW2 Cells

1998 ◽  
Vol 18 (6) ◽  
pp. 3278-3288 ◽  
Author(s):  
Dhaya Seshasayee ◽  
Peter Gaines ◽  
Don M. Wojchowski
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Receptor Gene ◽  
Globin Gene ◽  
Gene Activation ◽  
Embryonic Stem ◽  
Lineage Specification ◽  
Epo Receptor ◽  
Receptor Gene Expression

ABSTRACT Erythrocyte development has previously been shown to depend upon the expression of the lineage-restricted trans-acting factor GATA-1. Despite predicted roles for this factor during early development, GATA-1-deficient cells in chimeric mice and embryonic stem cell cultures mature to a late proerythroblast stage and express at least certain genes that normally are thought to be regulated by GATA-1 (including erythroid Krüppel-like factor [EKLF] and the erythropoietin [Epo] receptor). Opportunities to test roles for GATA-1 in erythroid gene activation in these systems therefore are limited. In the present study, in an alternate approach to test the function of GATA-1, GATA-1 has been expressed together with the Epo receptor in myeloid FDCW2 cells and the resulting effects on cytokine-dependent proliferation and erythroid gene expression have been assessed. GATA-1 expression at low levels delayed FDCW2ER cell cycle progression at the G1 phase specifically during Epo-induced mitogenesis. Upon expression of GATA-1 at increased levels, proliferation in response to Epo, interleukin-3 (IL-3), and stem cell factor was attenuated and endogenous GATA-1, EKLF and βmaj-globin gene expression was activated. Friend of GATA-1 (FOG) transcript levels also were enhanced, andets-1 and c-mpl but not Epo receptor gene expression was induced. Finally, in FDCW2 cells expressing increased levels of GATA-1 and a carboxyl-terminally truncated Epo receptor, Epo (with respect to IL-3 as a control) was shown to markedly promote globin transcript expression. Thus, novel evidence for select hierarchical roles for GATA-1 and Epo in erythroid lineage specification is provided.

Lipid droplet-associated gene expression and chromatin remodelling in LIPASE 5′-upstream region from beginning- to mid-endodormant bud in ‘Fuji’ apple

2017 ◽  
Vol 95 (4-5) ◽  
pp. 441-449 ◽  
Author(s):  
Takanori Saito ◽  
Shanshan Wang ◽  
Katsuya Ohkawa ◽  
Hitoshi Ohara ◽  
Hiromi Ikeura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Droplet ◽  
Chromatin Remodelling ◽  
Upstream Region ◽  
Fuji Apple
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