Unknown

Dataset Information

0

Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves gamma-globin activation by CREB1 and ATF-2.


ABSTRACT: The histone deacetylase inhibitors (HDA-CIs) butyrate and trichostatin A activate gamma-globin expression via a p38 mitogen-activating protein kinase (MAPK)-dependent mechanism. We hypothesized that down-stream effectors of p38 MAPK, namely activating transcription factor-2 (ATF-2) and cyclic AMP response element (CRE) binding protein (CREB), are intimately involved in fetal hemoglobin induction by these agents. In this study, we observed increased ATF-2 and CREB1 phosphorylation mediated by the HDACIs in K562 cells, in conjunction with histone H4 hyperacetylation. Moreover, enhanced DNA-protein interactions occurred in the CRE in the (G)gamma-globin promoter (G-CRE) in vitro after drug treatments; subsequent chromatin immunoprecipitation assay confirmed ATF-2 and CREB1 binding to the G-CRE in vivo. Enforced expression of ATF-2 and CREB produced (G)gamma-promoter trans-activation which was abolished by a 2-base pair mutation in the putative G-CRE. The data presented herein demonstrate that gamma-gene induction by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK signaling.

SUBMITTER: Sangerman J 

PROVIDER: S-EPMC1895433 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves gamma-globin activation by CREB1 and ATF-2.

Sangerman Jose J   Lee Moo Seung MS   Yao Xiao X   Oteng Eugene E   Hsiao Cheng-Hui CH   Li Wei W   Zein Sima S   Zein Sima S   Ofori-Acquah Solomon F SF   Pace Betty S BS  

Blood 20060808 10


The histone deacetylase inhibitors (HDA-CIs) butyrate and trichostatin A activate gamma-globin expression via a p38 mitogen-activating protein kinase (MAPK)-dependent mechanism. We hypothesized that down-stream effectors of p38 MAPK, namely activating transcription factor-2 (ATF-2) and cyclic AMP response element (CRE) binding protein (CREB), are intimately involved in fetal hemoglobin induction by these agents. In this study, we observed increased ATF-2 and CREB1 phosphorylation mediated by the  ...[more]

Similar Datasets

| S-EPMC3023528 | biostudies-literature
| S-EPMC4392404 | biostudies-literature
| S-EPMC6690964 | biostudies-literature
| S-EPMC7210980 | biostudies-literature
| S-EPMC8610173 | biostudies-literature
| S-EPMC2745848 | biostudies-literature
| S-EPMC8058333 | biostudies-literature
| S-EPMC2670570 | biostudies-literature
| S-EPMC9636226 | biostudies-literature
| S-EPMC6029722 | biostudies-literature