Overexpressed HIST1H2AC and ESR1:ESTG bind MYC and BCL2 genes

Stable Identifier
R-HSA-9011983
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

HIST1H2AC (also known as H2ac) is a replicative histone H2A isoform that is overexpressed in breast cancer (Shann et al, 2008). HIST1H2AC and HIST1H2AA, unique among HIST1H2 family members, contains a HAR domain that in yeast has been shown mediate interaction with histone H3 and to regulate gene expression (Zheng et al, 2010). Estrogen-dependent recruitment of HIST1H2AC to target genes contributes to the proliferative response to estrogen, and siRNA depletion of HIST1H2AC abrogates expression of genes including MYC, CCND1 and BCL2, among others, and results in cell cycle arrest at G0/G1. By ChIP, both the estrogen receptor and HIST1H2AC are present at distal enhancer elements and in the 3' UTR of target genes upon estrogen stimulation, and the proteins physically interact both in vitro and in vivo. HIST1H2AC and ESR1 contribute to target gene activation by promoting the formation of long distance chromatin loops between disparate regulatory regions (Su et al, 2013). Overexpression of HIST1H2AC additionally decreases the levels of the repressive epigenetic modification H3K9me2 that is associated with estrogen-responsive signaling, and HIST1H2AC contributes to the recruitment of the histone demethylase KDM1A (Perillo et al, 2008; Su et al, 2014).

Literature References
PubMed ID Title Journal Year
18256232 Genome-wide mapping and characterization of hypomethylated sites in human tissues and breast cancer cell lines

Shann, YJ, Cheng, C, Chiao, CH, Chen, DT, Li, PH, Hsu, MT

Genome Res. 2008
18187655 DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression

Perillo, B, Ombra, MN, Bertoni, A, Cuozzo, C, Sacchetti, S, Sasso, A, Chiariotti, L, Malorni, A, Abbondanza, C, Avvedimento, EV

Science 2008
24371278 An H2A histone isotype regulates estrogen receptor target genes by mediating enhancer-promoter-3'-UTR interactions in breast cancer cells

Su, CH, Tzeng, TY, Cheng, C, Hsu, MT

Nucleic Acids Res. 2014
20498280 Novel trans-tail regulation of H2B ubiquitylation and H3K4 methylation by the N terminus of histone H2A

Zheng, S, Wyrick, JJ, Reese, JC

Mol. Cell. Biol. 2010
Participants
Participant Of
Orthologous Events
Authored
Reviewed
Created