title: The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.
abstract: 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 regulatory networks involving BACH1, we combined chromatin immunoprecipitation sequencing analysis of BACH1 target genes in HEK 293 cells with knockdown of BACH1 using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays. The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. In addition to known and new BACH1 targets involved in heme degradation (HMOX1, FTL, FTH1, ME1, and SLC48A1) and redox regulation (GCLC, GCLM, and SLC7A11), we also discovered BACH1 target genes affecting cell cycle and apoptosis pathways (ITPR2, CALM1, SQSTM1, TFE3, EWSR1, CDK6, BCL2L11, and MAFG) as well as subcellular transport processes (CLSTN1, PSAP, MAPT, and 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.
authors.affiliation: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Warnatz
authors.forename: Dominic
authors.initials: D
authors.lastname: Schmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.forename: Ilaria
authors.initials: I
authors.lastname: Piccini
authors.forename: Marc
authors.initials: M
authors.lastname: Sultan
authors.forename: Tatiana
authors.initials: T
authors.lastname: Borodina
authors.forename: Daniela
authors.initials: D
authors.lastname: Balzereit
authors.forename: Wasco
authors.initials: W
authors.lastname: Wruck
authors.forename: Alexey
authors.initials: A
authors.lastname: Soldatov
authors.forename: Martin
authors.initials: M
authors.lastname: Vingron
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Yaspo
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology*; D020218:Response Elements / Q000502:physiology
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins