Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1.
Krüppel-like factor 1(KLF1) is a hematopoietic-specific zinc finger transcription factor essential for erythroid gene expression. In concert with the transacting factor GATA1, KLF1 modulates the coordinate expression of the genes encoding the multi-enzyme heme biosynthetic pathway during erythroid d...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3463598?pdf=render |
id |
doaj-826b227c2e0a40248347c4109d47e763 |
---|---|
record_format |
Article |
spelling |
doaj-826b227c2e0a40248347c4109d47e7632020-11-25T00:04:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4648210.1371/journal.pone.0046482Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1.Aurelie D DesgardinTatiana AbramovaTolulope O RosanwoSreedharan KarthaEun-Hee ShimStephen M JaneJohn M CunninghamKrüppel-like factor 1(KLF1) is a hematopoietic-specific zinc finger transcription factor essential for erythroid gene expression. In concert with the transacting factor GATA1, KLF1 modulates the coordinate expression of the genes encoding the multi-enzyme heme biosynthetic pathway during erythroid differentiation. To explore the mechanisms underpinning KLF1 action at the gene loci regulating the first 3 steps in this process, we have exploited the K1-ERp erythroid cell line, in which KLF1 translocates rapidly to the nucleus in response to treatment with 4-OH-Tamoxifen (4-OHT). KLF1 acts as a differentiation-independent transcriptional co-regulator of delta-aminolevulinic acid dehydratase (Alad), but not 5-aminolevulinate synthase gene (Alas2) or porphobilinogen deaminase (Pbgd). Similar to its role at the β-globin promoter, KLF1 induces factor recruitment and chromatin changes at the Alad1b promoter in a temporally-specific manner. In contrast to these changes, we observed a distinct mechanism of histone eviction at the Alad1b promoter. Furthermore, KLF1-dependent events were not modulated by GATA1 factor promoter co-occupancy alone. These results not only enhance our understanding of erythroid-specific modulation of heme biosynthetic regulation by KLF1, but provide a model that will facilitate the elucidation of novel KLF1-dependent events at erythroid gene loci that are independent of GATA1 activity.http://europepmc.org/articles/PMC3463598?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aurelie D Desgardin Tatiana Abramova Tolulope O Rosanwo Sreedharan Kartha Eun-Hee Shim Stephen M Jane John M Cunningham |
spellingShingle |
Aurelie D Desgardin Tatiana Abramova Tolulope O Rosanwo Sreedharan Kartha Eun-Hee Shim Stephen M Jane John M Cunningham Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. PLoS ONE |
author_facet |
Aurelie D Desgardin Tatiana Abramova Tolulope O Rosanwo Sreedharan Kartha Eun-Hee Shim Stephen M Jane John M Cunningham |
author_sort |
Aurelie D Desgardin |
title |
Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. |
title_short |
Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. |
title_full |
Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. |
title_fullStr |
Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. |
title_full_unstemmed |
Regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. |
title_sort |
regulation of delta-aminolevulinic acid dehydratase by krüppel-like factor 1. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Krüppel-like factor 1(KLF1) is a hematopoietic-specific zinc finger transcription factor essential for erythroid gene expression. In concert with the transacting factor GATA1, KLF1 modulates the coordinate expression of the genes encoding the multi-enzyme heme biosynthetic pathway during erythroid differentiation. To explore the mechanisms underpinning KLF1 action at the gene loci regulating the first 3 steps in this process, we have exploited the K1-ERp erythroid cell line, in which KLF1 translocates rapidly to the nucleus in response to treatment with 4-OH-Tamoxifen (4-OHT). KLF1 acts as a differentiation-independent transcriptional co-regulator of delta-aminolevulinic acid dehydratase (Alad), but not 5-aminolevulinate synthase gene (Alas2) or porphobilinogen deaminase (Pbgd). Similar to its role at the β-globin promoter, KLF1 induces factor recruitment and chromatin changes at the Alad1b promoter in a temporally-specific manner. In contrast to these changes, we observed a distinct mechanism of histone eviction at the Alad1b promoter. Furthermore, KLF1-dependent events were not modulated by GATA1 factor promoter co-occupancy alone. These results not only enhance our understanding of erythroid-specific modulation of heme biosynthetic regulation by KLF1, but provide a model that will facilitate the elucidation of novel KLF1-dependent events at erythroid gene loci that are independent of GATA1 activity. |
url |
http://europepmc.org/articles/PMC3463598?pdf=render |
work_keys_str_mv |
AT aurelieddesgardin regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 AT tatianaabramova regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 AT tolulopeorosanwo regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 AT sreedharankartha regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 AT eunheeshim regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 AT stephenmjane regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 AT johnmcunningham regulationofdeltaaminolevulinicaciddehydratasebykruppellikefactor1 |
_version_ |
1725428485614206976 |