HIV-1-derived self-inactivating lentivirus vector induces megakaryocyte lineage-specific gene expression

2005 ◽  
Vol 7 (2) ◽  
pp. 240-247 ◽  
Author(s):  
Kazuta Yasui ◽  
Rika A. Furuta ◽  
Kayoko Matsumoto ◽  
Yoshihiko Tani ◽  
Jun-ichi Fujisawa
Keyword(s):  
Gene Expression ◽  
Specific Gene ◽  
Lentivirus Vector ◽  
Specific Gene Expression ◽  
Lineage Specific Gene ◽  
Hiv 1

scholarly journals Dynamic changes in cis-regulatory occupancy by Six1 and its cooperative interactions with distinct cofactors drive lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium

2020 ◽  
Vol 48 (6) ◽  
pp. 2880-2896 ◽  
Author(s):  
Jun Li ◽  
Ting Zhang ◽  
Aarthi Ramakrishnan ◽  
Bernd Fritzsch ◽  
Jinshu Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Sensory Epithelium ◽  
Hair Bundle ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Wide Range ◽  
Cell Type Specific ◽  
Lineage Specific Gene

Abstract The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1’s downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one of the most significantly enriched motifs in Six1-bound sites, and we demonstrate that Six1-RFX proteins cooperatively regulate gene expression through binding to SIX:RFX-motifs. Six1 targets a wide range of hair-bundle regulators and late Six1 deletion disrupts hair-bundle polarity. This study provides a mechanistic understanding of how Six1 cooperates with distinct cofactors in feedforward loops to control lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.

scholarly journals Microarray Analysis of Lymphatic Tissue Reveals Stage-Specific, Gene Expression Signatures in HIV-1 Infection

2009 ◽  
Vol 183 (3) ◽  
pp. 1975-1982 ◽  
Author(s):  
Qingsheng Li ◽  
Anthony J. Smith ◽  
Timothy W. Schacker ◽  
John V. Carlis ◽  
Lijie Duan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Specific Gene ◽  
Lymphatic Tissue ◽  
Specific Gene Expression ◽  
Gene Expression Signatures ◽  
Hiv 1

Characterization of hematopoietic lineage-specific gene expression by ES cell in vitro differentiation induction system

Blood ◽  
2000 ◽  
Vol 95 (3) ◽  
pp. 870-878 ◽  
Author(s):  
Takumi Era ◽  
Toshiaki Takagi ◽  
Tomomi Takahashi ◽  
Jean-Christophe Bories ◽  
Toru Nakano
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Embryonic Stem ◽  
Experimental System ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Differentiation Induction ◽  
Lineage Specific Gene ◽  
Megakaryocytic Cell

The continuous generation of mature blood cells from hematopoietic progenitor cells requires a highly complex series of molecular events. To examine lineage-specific gene expression during the differentiation process, we developed a novel method combiningLacZ reporter gene analysis with in vitro hematopoietic differentiation induction from mouse embryonic stem cells. For a model system using this method, we chose the erythroid and megakaryocytic differentiation pathways. Although erythroid and megakaryocytic cells possess distinct functional and morphologic features, these 2 lineages originate from bipotential erythro-megakaryocytic progenitors and share common lineage-restricted transcription factors. A portion of the 5′ flanking region of the human glycoprotein IIb (IIb) integrin gene extending from base −598 to base +33 was examined in detail. As reported previously, this region is sufficient for megakaryocyte-specific gene expression. However, previous reports that used human erythro-megakaryocytic cell lines suggested that one or more negative regulatory regions were necessary for megakaryocyte-specific gene expression. Our data clearly showed that an approximately 200-base enhancer region extending from −598 to −400 was sufficient for megakaryocyte-specific gene expression. This experimental system has advantages over those using erythro-megakaryocytic cell lines because it recapitulates normal hematopoietic cell development and differentiation. Furthermore, this system is more efficient than transgenic analysis and can easily examine gene expression with null mutations of specific genes.

Coordinating Self-Renewal and Proliferation via MLL1-HOX Pathways and Beyond

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-28-SCI-28
Author(s):  
Patricia Ernst ◽  
Erika L. Artinger ◽  
Bibhu P. Mishra ◽  
Kristin M. Zaffuto ◽  
Bin E. Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcriptional Regulators ◽  
Conditional Knockout ◽  
Specific Gene ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Specific Gene Expression ◽  
Lineage Specific Gene

Abstract Abstract SCI-28 Epigenetic regulation of gene expression plays a central role in normal hematopoietic stem cell (HSC) maintenance and leukemogenesis. The histone methyltransferase, MLL1, is essential for the maintenance of HSCs and is a common target of chromosomal translocations that result in acute leukemia. To discover genetic networks regulated by MLL1 in HSCs, we identified genes that were acutely deregulated upon Mll1 loss in HSCs, using a conditional knockout approach and lineage-negative, c-Kit+, Sca-1+, CD48-negative (LSK/CD48neg) cells. The majority of genes that changed were proliferation-associated genes, upregulated in Mll1−/− LSK/CD48neg cells. This reflected the fact that Mll1-deficient HSCs exhibit increased proliferation in vivo, a phenotype previously documented using the Mx1-cre inducible model. To determine whether the increased proliferation was cell-intrinsic, we performed single cell proliferation studies in serum-free medium containing SCF, IL-11, and Flt3L. We found that Mll1−/− LSK/CD48neg single cells entered the cell cycle earlier and that each cell cycle was shorter than wild-type controls. Evidence for failure to suppress lineage-specific gene expression was also observed; specifically, five percent of the upregulated genes encoded erythroid-specific proteins. These included erythroid transcriptional regulators such as GATA1 and KLF1, but also structural proteins such as spectrin, KEL, and EpoR. The relationship between erythroid-lineage genes and Mll1 was unique, since no other lineage-specific programs were upregulated in Mll1−/− LSK/CD48neg cells. Among the genes downregulated upon Mll1 loss, the largest category was comprised of transcriptional regulators, including Mecom, Pbx1, and Prdm16, which are known to control HSC self-renewal and quiescence. As observed in many other tissues, Mll1−/− LSK/CD48neg cells also exhibited reduced Hoxa9 expression. Interestingly, not all identified MLL1 target genes required menin, a cofactor thought to participate in directing MLL1 to particular genomic loci in vivo, and not all targets were Mll1-dependent in nonhematopoietic tissues. Chromatin immunoprecipitation and functional studies suggest that the identified genes act within a series of parallel pathways as direct transcriptional targets of MLL1. Interestingly, reexpression of Prdm16 alone could rescue Mll1-deficient cells from rapid attrition in bone marrow chimeras. Furthermore, Prdm16 corrected the hyperproliferation phenotype of Mll1−/− LSK/CD48neg cells. These data demonstrate that MLL1 coordinately regulates proliferation, lineage-specific gene expression programs, and self-renewal. By elucidating the normal MLL1-dependent transcriptional network within HSCs, we show that this pathway is overlapping but distinguishable from the leukemogenic pathway, suggesting that targeted therapy with minimal side effects on hematopoiesis will be feasible. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cofactor-Mediated Restriction of GATA-1 Chromatin Occupancy Coordinates Lineage-Specific Gene Expression

2012 ◽  
Vol 47 (4) ◽  
pp. 608-621 ◽  
Author(s):  
Timothy M. Chlon ◽  
Louis C. Doré ◽  
John D. Crispino
Keyword(s):  
Gene Expression ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Lineage Specific Gene
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