KLF1 directly activates expression of the novel fetal globin repressor ZBTB7A/LRF in erythroid cells

Blood Advances
Laura J NortonMerlin Crossley

Abstract

Genes encoding the human β-like hemoglobin proteins undergo a developmental switch from fetal γ-globin to adult β-globin expression around the time of birth. β-hemoglobinopathies, such as sickle-cell disease and β-thalassemia, result from mutations affecting the adult β-globin gene. The only treatment options currently available carry significant adverse effects. Analyses of heritable variations in fetal hemoglobin (HbF) levels have provided evidence that reactivation of the silenced fetal γ-globin genes in adult erythroid cells is a promising therapy. The γ-globin repressor BCL11A has become the major focus, with several studies investigating its regulation and function as a first step to inhibiting its expression or activity. However, a second repression mechanism was recently shown to be mediated by the transcription factor ZBTB7A/LRF, suggesting that understanding the regulation of ZBTB7A may also be useful. Here we show that Krüppel-like factor 1 (KLF1) directly drives expression of ZBTB7A in erythroid cells by binding to its proximal promoter. We have also uncovered an erythroid-specific regulation mechanism, leading to the upregulation of a novel ZBTB7A transcript in the erythroid compartment. The demonstration that ZBTB...Continue Reading

References

Mar 1, 1976·British Journal of Haematology·S FriedmanV Ahern
Feb 3, 2005·Molecular and Cellular Biology·José PerdomoMerlin Crossley
Dec 29, 2005·Blood·Denise HodgeAndrew Perkins
Feb 7, 2007·Molecular and Cellular Biology·Alister P W FunnellMerlin Crossley
May 17, 2007·Blood·Laura GutiérrezBart N Lambrecht
Feb 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Manuela UdaAntonio Cao
Aug 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Guillaume LettreStuart H Orkin
Mar 12, 2009·Methods : a Companion to Methods in Enzymology·Dominic SchmidtDuncan T Odom
May 29, 2010·Genome Research·Michael R TallackAndrew C Perkins
Aug 3, 2010·Nature Genetics·Dewang ZhouTim M Townes
Mar 29, 2014·Nature·Alistair R R ForrestYoshihide Hayashizaki
Feb 28, 2015·Genome Biology·Marina LizioUNKNOWN FANTOM consortium

❮ Previous
Next ❯

Citations

Nov 15, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jin KangAeRi Kim
Feb 1, 2019·Molecular Diagnosis & Therapy·Valentina GhiaccioLaura Breda
Mar 29, 2019·PloS One·Ileana CantúThamar B van Dijk
Jul 1, 2017·Blood·Beeke WienertMerlin Crossley
Dec 12, 2019·Human Genomics·Caterina ConstantinouArgyro Sgourou
Jan 27, 2019·Journal of Pharmaceutical Investigation·Seok-Beom YongYong-Hee Kim
Aug 19, 2020·Blood·Martin H Steinberg
May 30, 2020·Haematologica·Anne KorporaalSjaak Philipsen
Apr 30, 2020·Cancer Letters·Sanjay GuptaShashank Kumar
Oct 15, 2020·International Journal of Molecular Sciences·Giulia BreveglieriMonica Borgatti
Feb 26, 2021·Current Opinion in Hematology·Eugene Khandros, Gerd A Blobel
Apr 4, 2021·International Journal of Molecular Sciences·Panayiota L PapasavvaCarsten W Lederer
Jun 23, 2021·JCI Insight·Kazufumi MatsushitaStephen J Galli
Aug 17, 2021·Journal of Clinical Laboratory Analysis·Haiwei WangLiangpu Xu
Nov 25, 2021·Science Advances·Richard KingRami Khoriaty

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.