Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide map of BACH1 binding in HEK 293T cells


ABSTRACT: BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we combined chromatin immunoprecipitation-sequencing (ChIP-seq) analysis of BACH1 target genes in HEK 293 cells with knock-down of BACH1 using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays. The 59 BACH1 target genes identified by ChIP-seq were found highly enriched in genes showing expression changes after BACH1 knock-down, demonstrating the impact of BACH1 repression on transcription. In addition to known and new BACH1 targets involved in heme degradation (HMOX1, FTL, FTH1, ME1, SLC48A1) and redox regulation (GCLC, GCLM, SLC7A11), we also discovered BACH1 target genes effecting cell cycle and apoptosis pathways (ITPR2, CALM1, SQSTM1, TFE3, EWSR1, CDK6, BCL2L11, MAFG) as well as subcellular transport processes (CLSTN1, PSAP, MAPT, vault RNA). The newly identified impact of BACH1 on genes involved in neurodegenerative processes and proliferation provides an interesting basis for future dissection of BACH1-mediated gene repression in neurodegeneration and virus-induced cancerogenesis. Examination of BACH1 binding in HEK 293T cells by chromatin immunoprecipitation-sequencing (CHIP-seq) with input DNA as control.

ORGANISM(S): Homo sapiens

SUBMITTER: Hans-Jörg Warnatz 

PROVIDER: E-GEOD-28051 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.

Warnatz Hans-Jörg HJ   Schmidt Dominic D   Manke Thomas T   Piccini Ilaria I   Sultan Marc M   Borodina Tatiana T   Balzereit Daniela D   Wruck Wasco W   Soldatov Alexey A   Vingron Martin M   Lehrach Hans H   Yaspo Marie-Laure ML  

The Journal of biological chemistry 20110509 26


The regulation of gene expression in response to environmental signals and metabolic imbalances is a key step in maintaining cellular homeostasis. BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAF recognition elements, resulting in increased expression of antioxidant response genes. To systematically address the gene regula  ...[more]

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