Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells.
Enhancer of zest homolog 2 (EZH2) is a histone methyltransferase which plays a crucial role in cancer progression by regulation of genes involved in cellular processes such as proliferation, invasion and self-renewal. Activity and biological function of EZH2 are regulated by posttranslational modifi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5986130?pdf=render |
| _version_ | 1811211916862816256 |
|---|---|
| author | Ewa Forma Paweł Jóźwiak Piotr Ciesielski Agnieszka Zaczek Katarzyna Starska Magdalena Bryś Anna Krześlak |
| author_facet | Ewa Forma Paweł Jóźwiak Piotr Ciesielski Agnieszka Zaczek Katarzyna Starska Magdalena Bryś Anna Krześlak |
| author_sort | Ewa Forma |
| collection | DOAJ |
| description | Enhancer of zest homolog 2 (EZH2) is a histone methyltransferase which plays a crucial role in cancer progression by regulation of genes involved in cellular processes such as proliferation, invasion and self-renewal. Activity and biological function of EZH2 are regulated by posttranslational modifications. It is suggested that EZH2 stability may be regulated by O-GlcNAc transferase (OGT), which is an enzyme catalyzing the addition of GlcNAc moieties to target proteins. In this study, we determined the impact of OGT on expression of EZH2 target genes FOXA1 and FOXC1, that are involved in breast cancer progression. The results of chromatin immunoprecipitation experiments showed that both EZH2 and OGT are targeted to the promoter regions of FOXA1 and FOXC1 and knockdown of EZH2 or OGT affects expression of studied genes in breast non-malignant (MCF10A) and cancer cells (MCF7, T47D and MDA-MB-231). The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability. |
| first_indexed | 2024-04-12T05:20:22Z |
| format | Article |
| id | doaj.art-8fbd3463e58547889c7d2b4c9ae91141 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:20:22Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8fbd3463e58547889c7d2b4c9ae911412022-12-22T03:46:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019835110.1371/journal.pone.0198351Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells.Ewa FormaPaweł JóźwiakPiotr CiesielskiAgnieszka ZaczekKatarzyna StarskaMagdalena BryśAnna KrześlakEnhancer of zest homolog 2 (EZH2) is a histone methyltransferase which plays a crucial role in cancer progression by regulation of genes involved in cellular processes such as proliferation, invasion and self-renewal. Activity and biological function of EZH2 are regulated by posttranslational modifications. It is suggested that EZH2 stability may be regulated by O-GlcNAc transferase (OGT), which is an enzyme catalyzing the addition of GlcNAc moieties to target proteins. In this study, we determined the impact of OGT on expression of EZH2 target genes FOXA1 and FOXC1, that are involved in breast cancer progression. The results of chromatin immunoprecipitation experiments showed that both EZH2 and OGT are targeted to the promoter regions of FOXA1 and FOXC1 and knockdown of EZH2 or OGT affects expression of studied genes in breast non-malignant (MCF10A) and cancer cells (MCF7, T47D and MDA-MB-231). The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability.http://europepmc.org/articles/PMC5986130?pdf=render |
| spellingShingle | Ewa Forma Paweł Jóźwiak Piotr Ciesielski Agnieszka Zaczek Katarzyna Starska Magdalena Bryś Anna Krześlak Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells. PLoS ONE |
| title | Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells. |
| title_full | Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells. |
| title_fullStr | Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells. |
| title_full_unstemmed | Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells. |
| title_short | Impact of OGT deregulation on EZH2 target genes FOXA1 and FOXC1 expression in breast cancer cells. |
| title_sort | impact of ogt deregulation on ezh2 target genes foxa1 and foxc1 expression in breast cancer cells |
| url | http://europepmc.org/articles/PMC5986130?pdf=render |
| work_keys_str_mv | AT ewaforma impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells AT pawełjozwiak impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells AT piotrciesielski impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells AT agnieszkazaczek impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells AT katarzynastarska impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells AT magdalenabrys impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells AT annakrzeslak impactofogtderegulationonezh2targetgenesfoxa1andfoxc1expressioninbreastcancercells |