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Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40). Knockdown of FACT or RNF20/40 expression leads to decreased transcription initiation and elongation at HIF-1 target genes. Mechanistically, FACT and RNF20/40 are recruited to hypoxia response elements (HREs) by HIF-1 and stabilize binding of HIF-1 (and each other) at HREs. Hypoxia induces the monoubiquitination of histone H2B at lysine 120 at HIF-1 target genes in an HIF-1-dependent manner. Together, these findings delineate a cooperative molecular mechanism by which FACT and RNF20/40 stabilize multiprotein complex formation at HREs and mediate histone ubiquitination to facilitate HIF-1 transcriptional activity.
Pubmed ID: 38517892 RIS Download
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This monoclonal secondary targets IgG
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis unknown targets RNF40
View all literature mentionsThis polyclonal targets HIF-1 beta
View all literature mentionsThis unknown targets HIF-1 alpha
View all literature mentionsThis polyclonal secondary targets not applicable
View all literature mentionsThis unknown targets Normal Goat IgG
View all literature mentionsThis unknown targets Rabbit Normal igg Control antibody
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis polyclonal targets V5 Epitope Tag
View all literature mentionsThis polyclonal targets V5 Epitope Tag
View all literature mentionsThis monoclonal targets Goat IgG
View all literature mentionsThis monoclonal targets Ubiquityl-Histone H2B (Lys120) (D11) XP Rabbit mAb
View all literature mentionsThis polyclonal targets RNF40
View all literature mentionsThis polyclonal targets RNF20
View all literature mentionsThis monoclonal targets SSRP1
View all literature mentionsThis polyclonal targets Human SUPT16H
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets HIF-1α
View all literature mentionsThis monoclonal targets HIF-1a
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUM159PT is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUM159PT is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis unknown targets RNF40
View all literature mentionsThis polyclonal targets HIF-1 beta
View all literature mentionsThis unknown targets HIF-1 alpha
View all literature mentionsThis polyclonal secondary targets not applicable
View all literature mentionsThis unknown targets Normal Goat IgG
View all literature mentionsThis unknown targets Rabbit Normal igg Control antibody
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis polyclonal targets V5 Epitope Tag
View all literature mentionsThis polyclonal targets V5 Epitope Tag
View all literature mentionsThis monoclonal targets Goat IgG
View all literature mentionsThis monoclonal targets Ubiquityl-Histone H2B (Lys120) (D11) XP Rabbit mAb
View all literature mentionsThis polyclonal targets RNF40
View all literature mentionsThis polyclonal targets RNF20
View all literature mentionsThis monoclonal targets SSRP1
View all literature mentionsThis polyclonal targets Human SUPT16H
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets HIF-1α
View all literature mentionsThis monoclonal targets HIF-1a
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