About: Epigenetic Control of SPI1 Gene by CTCF and ISWI ATPase SMARCA5     Goto   Sponge   Distinct   Permalink

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Description
  • CCCTC-binding factor (CTCF) can both activate as well as inhibit transcription by forming chromatin loops between regulatory regions and promoters. In this regard, Ctcf binding on non-methylated DNA and its interaction with the Cohesin complex results in differential regulation of the H19/Igf2 locus. Similarly, a role for CTCF has been established in normal hematopoietic development; however its involvement in leukemia remains elusive. Here, we show that Ctcf binds to the imprinting control region of H19/Igf2 in AML blasts. We also demonstrate that Smarca5, which also associates with the Cohesin complex, facilitates Ctcf binding to its target sites on DNA. Furthermore, Smarca5 supports Ctcf functionally and is needed for enhancer-blocking effect at ICR. We next asked whether CTCF and SMARCA5 control the expression of key hematopoiesis regulators. In normally differentiating myeloid cells both CTCF and SMARCA5 together with members of the Cohesin complex are recruited to the SPI1 gene, a key hematopoiesis regulator and leukemia suppressor. Due to DNA methylation, CTCF binding to the SPI1 gene is blocked in AML blasts. Upon AZA-mediated DNA demethylation of human AML blasts, CTCF and SMARCA5 are recruited to the -14.4 Enhancer of SPI1 gene and block its expression. Our data provide new insight into complex SPI1 gene regulation now involving additional key epigenetic factors, CTCF and SMARCA5 that control PU. 1 expression at the -14.4 Enhancer.
  • CCCTC-binding factor (CTCF) can both activate as well as inhibit transcription by forming chromatin loops between regulatory regions and promoters. In this regard, Ctcf binding on non-methylated DNA and its interaction with the Cohesin complex results in differential regulation of the H19/Igf2 locus. Similarly, a role for CTCF has been established in normal hematopoietic development; however its involvement in leukemia remains elusive. Here, we show that Ctcf binds to the imprinting control region of H19/Igf2 in AML blasts. We also demonstrate that Smarca5, which also associates with the Cohesin complex, facilitates Ctcf binding to its target sites on DNA. Furthermore, Smarca5 supports Ctcf functionally and is needed for enhancer-blocking effect at ICR. We next asked whether CTCF and SMARCA5 control the expression of key hematopoiesis regulators. In normally differentiating myeloid cells both CTCF and SMARCA5 together with members of the Cohesin complex are recruited to the SPI1 gene, a key hematopoiesis regulator and leukemia suppressor. Due to DNA methylation, CTCF binding to the SPI1 gene is blocked in AML blasts. Upon AZA-mediated DNA demethylation of human AML blasts, CTCF and SMARCA5 are recruited to the -14.4 Enhancer of SPI1 gene and block its expression. Our data provide new insight into complex SPI1 gene regulation now involving additional key epigenetic factors, CTCF and SMARCA5 that control PU. 1 expression at the -14.4 Enhancer. (en)
Title
  • Epigenetic Control of SPI1 Gene by CTCF and ISWI ATPase SMARCA5
  • Epigenetic Control of SPI1 Gene by CTCF and ISWI ATPase SMARCA5 (en)
skos:prefLabel
  • Epigenetic Control of SPI1 Gene by CTCF and ISWI ATPase SMARCA5
  • Epigenetic Control of SPI1 Gene by CTCF and ISWI ATPase SMARCA5 (en)
skos:notation
  • RIV/00216208:11110/14:10282399!RIV15-MSM-11110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(ED1.1.00/02.0109), P(GAP305/12/1033), S
http://linked.open...iv/cisloPeriodika
  • 2
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 14853
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11110/14:10282399
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • insulator; cells; cohesin; methylation; leukemia; expression; differentiation; pu.1; transcription-factor; chromatin remodeling complex (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [27011EC1E353]
http://linked.open...i/riv/nazevZdroje
  • PLoS ONE
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 9
http://linked.open...iv/tvurceVysledku
  • Stopka, Tomáš
  • Jonášová, Anna
  • Zikmund, Tomáš
  • Čuřík, Nikola
  • Vargová, Jarmila
  • Dluhošová, Martina
http://linked.open...ain/vavai/riv/wos
  • 000330626900070
issn
  • 1932-6203
number of pages
http://bibframe.org/vocab/doi
  • 10.1371/journal.pone.0087448
http://localhost/t...ganizacniJednotka
  • 11110
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