The Human GATA1 Gene Retains a 5' Insulator That Maintains Chromosomal Architecture and GATA1 Expression Levels in Splenic Erythroblasts

Molecular and Cellular Biology
Takashi MoriguchiMasayuki Yamamoto

Abstract

GATA1 is a key transcription factor for erythropoiesis. GATA1 gene expression is strictly regulated at the transcriptional level. While the regulatory mechanisms governing mouse Gata1 (mGata1) gene expression have been studied extensively, how expression of the human GATA1 (hGATA1) gene is regulated remains to be elucidated. To address this issue, we generated hGATA1 bacterial artificial chromosome (BAC) transgenic mouse lines harboring a 183-kb hGATA1 locus covering the hGATA1 exons and distal flanking sequences. Transgenic hGATA1 expression coincides with endogenous mGata1 expression and fully rescues hematopoietic deficiency in mGata1 knockdown mice. The transgene exhibited copy number-dependent and integration position-independent expression of hGATA1, indicating the presence of chromatin insulator activity within the transgene. We found a novel insulator element at 29 kb 5' to the hGATA1 gene and refer to this element as the 5' CCCTC-binding factor (CTCF) site. Substitution mutation of the 5' CTCF site in the hGATA1 BAC disrupted the chromatin architecture and led to a reduction of hGATA1 expression in splenic erythroblasts under conditions of stress erythropoiesis. Our results demonstrate that expression of the hGATA1 gen...Continue Reading

References

Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·K OnoderaM Yamamoto
May 9, 1997·The Journal of Biological Chemistry·S TakahashiM Yamamoto
Feb 1, 1997·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·M YamamotoJ D Engel
Dec 18, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kinuko OhnedaMasayuki Yamamoto
Feb 3, 2005·Molecular and Cellular Biology·Rita FerreiraSjaak Philipsen
Jun 22, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Naoko MinegishiMasayuki Yamamoto
Aug 16, 2006·Nature Reviews. Genetics·Miklos Gaszner, Gary Felsenfeld
Jan 16, 2007·Molecular Cell·Alexander J RuthenburgJoanna Wysocka
Jul 21, 2007·Nature Protocols·Hélène HagègeThierry Forné
Feb 1, 2008·Nature·Kerstin S WendtJan-Michael Peters
Mar 21, 2008·Nature Reviews. Cancer·Ritsuko ShimizuMasayuki Yamamoto
Dec 24, 2008·Molecular and Cellular Biology·Mikiko SuzukiMasayuki Yamamoto
Mar 11, 2010·Current Opinion in Hematology·Hiroshi KanekoMasayuki Yamamoto
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Nov 30, 2012·Nucleic Acids Research·Jesse D ZiebarthYan Cui
Aug 6, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Mikiko SuzukiMasayuki Yamamoto
Oct 15, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ritsuko ShimizuMasayuki Yamamoto
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Novalia PisheshaHarvey F Lodish
Mar 19, 2014·International Journal of Hematology·Takashi Moriguchi, Masayuki Yamamoto
Nov 21, 2014·Science·Jeff VierstraJohn A Stamatoyannopoulos
Dec 24, 2014·Molecular and Cellular Biology·Takashi MoriguchiMasayuki Yamamoto

❮ Previous
Next ❯

Citations

Jan 3, 2016·Experimental Hematology·Isuzu KobayashiWataru Nunomura
Apr 15, 2015·Molecular and Cellular Biology·Petros PapadopoulosLàszlò Tora

❮ Previous
Next ❯

Related Concepts

Related Feeds

Artificial Chromosomes

Artificial chromosomes are genetically engineered chromosomes derived from the DNA of a species. Discover the latest research on artificial chromosomes here.