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Muc1-C Induces Pbrm1-Mediated Chromatin Remodeling in Driving Chronic Inflammation and DNA Damage Resistance in Triple-Negative Breast Cancer

ABSTRACT: Muc1-C Induces Pbrm1-Mediated Chromatin Remodeling in Driving Chronic Inflammation and DNA Damage Resistance in Triple-Negative Breast Cancer

PROVIDER: PRJNA849622 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19664677_1.fastq.gz	Fastqsanger.gz
	SRR19664677_2.fastq.gz	Fastqsanger.gz
	SRR19664678_1.fastq.gz	Fastqsanger.gz
	SRR19664678_2.fastq.gz	Fastqsanger.gz
	SRR19664679_1.fastq.gz	Fastqsanger.gz

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MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [tet-MUC1 shRNA]

Project description:STAT1 and IRF1 are essential effectors of the type I and II interferon (IFN) pathways. Here, we report that the oncogenic MUC1-C protein is necessary for inducing chromatin accessibility and activation of the STAT1 and IRF1 genes in triple-negative breast cancer (TNBC) cells. Our results demonstrate that MUC1-C activates the PBRM1 subunit of the SWI/SNF PBAF chromatin remodeling complex and forms a nuclear complex with PBRM1. We show that MUC1-C associates with PBRM1 and STAT1 on the IRF1 gene at (i) a proximal enhancer-like signature (PLS), and (ii) distal enhancer-like signatures (dELSs). We also show MUC1-C and PBRM1 are necessary for opening chromatin at these signatures and for the induction of IRF1 expression. In extending these results, we found that MUC1-C binds directly to IRF1 and forms nuclear complexes with PBRM1 and IRF1, which are necessary for inducing chromatin accessibility at PLS of the (i) STAT1 gene, (ii) type II IFN pathway IDO1 and WARS genes, and (iii) type I IFN pathway RIG-I, MDA5 and ISG15 genes. Consistent with involvement of chronic inflammation in promoting the cancer stem cell (CSC) state, we show that MUC1-C, PBRM1 and IRF1 are required for self-renewal of TNBC CSCs. Of translational relevance, we report that targeting MUC1-C, PBRM1 and IRF1 circumvents intrinsic DNA damage resistance of TNBC CSCs and that MUC1-C is necessary for acquired resistance to the PARP inhibitor olaparib. These findings demonstrate that MUC1-C activates PBRM1/IRF1 and thereby chromatin remodeling of IFN pathway genes that promote chronic inflammation, the CSC state and DNA damage resistance.

2023-06-14 | GSE212587 | GEO

Muc1-C Induces Pbrm1-Mediated Chromatin Remodeling in Driving Chronic Inflammation and DNA Damage Resistance in Triple-Negative Breast Cancer

Project description:STAT1 and IRF1 are essential effectors of the type I and II interferon (IFN) pathways. Here, we report that the oncogenic MUC1-C protein is necessary for inducing chromatin accessibility and activation of the STAT1 and IRF1 genes in triple-negative breast cancer (TNBC) cells. Our results demonstrate that MUC1-C activates the PBRM1 subunit of the SWI/SNF PBAF chromatin remodeling complex and forms a nuclear complex with PBRM1. We show that MUC1-C associates with PBRM1 and STAT1 on the IRF1 gene at (i) a proximal enhancer-like signature (pELS), and (ii) distal enhancer-like signatures (dELSs). We also show MUC1-C and PBRM1 are necessary for opening chromatin at these signatures and for the induction of IRF1 expression. In extending these results, we found that MUC1-C binds directly to IRF1 and forms nuclear complexes with PBRM1 and IRF1, which are necessary for inducing chromatin accessibility at pELSs of the (i) STAT1 gene, (ii) type II IFN pathway IDO1 and WARS genes, and (iii) type I IFN pathway RIG-I, MDA5 and ISG15 genes. Consistent with involvement of chronic inflammation in promoting the cancer stem cell (CSC) state, we show that MUC1-C, PBRM1 and IRF1 are required for self-renewal of TNBC CSCs. Of translational relevance, we report that targeting MUC1-C, PBRM1 and IRF1 circumvents intrinsic DNA damage resistance of TNBC CSCs and that MUC1-C is necessary for acquired resistance to the PARP inhibitor olaparib. These findings demonstrate that MUC1-C activates PBRM1 and thereby chromatin remodeling of IFN pathway genes that promote chronic inflammation, the CSC state and DNA damage resistance.

2022-06-21 | GSE206212 | GEO

MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [BT549_shPBRM1]

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MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [BT549_shIRF1]

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MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [tet-MUC1 shRNA]

Project description:MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [tet-MUC1 shRNA]

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MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER

Project description:MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER

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MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [BT549_shIRF1]

Project description:MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [BT549_shIRF1]

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MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [BT549_shPBRM1]

Project description:MUC1-C INDUCES PBRM1-MEDIATED CHROMATIN REMODELING IN DRIVING CHRONIC INFLAMMATION AND DNA DAMAGE RESISTANCE IN TRIPLE-NEGATIVE BREAST CANCER [BT549_shPBRM1]

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MUC1-C ACTIVATES THE NURD COMPLEX IN DEDIFFERENTIATION OF TRIPLE-NEGATIVE BREASTCANCER CELLS

Project description:The NuRD chromatin remodeling and deacetylation complex, which includes MTA1, MBD3, CHD4 and HDAC1 among other components, is of importance for development and cancer progression. The oncogenic MUC1-C protein activates EZH2 and BMI1 in the epigenetic reprogramming of triple-negative breast cancer (TNBC) cells. However, there is no known link between MUC1-C and chromatin remodeling complexes. The present studies demonstrate that MUC1-C binds directly to the MYC HLH/LZ domain. In turn, we identified a previously unrecognized MUC1-C®MYC pathway that regulates the NuRD complex. We show that MUC1-C/MYC complexes selectively activate the MTA1 and MBD3 genes and posttranscriptionally induce CHD4 expression in basal- and not luminal-type BC cells. The results further show that MUC1-C forms complexes with these NuRD components on the ESR1 promoter. In this way, silencing MUC1-C (i) decreased MTA1/MBD3/CHD4/HDAC1 occupancy and increased H3K27 acetylation on the ESR1 promoter, and (ii) induced ESR1 expression and downstream estrogen response pathways. We also demonstrate that targeting MUC1-C and these NuRD components induces expression of FOXA1, GATA3 and other markers associated with the luminal phenotype. These findings and results from gain-of-function studies support a model in which MUC1-C activates the NuRD complex in driving luminal®basal dedifferentiation and plasticity of TNBC cells.

2020-03-05 | GSE134147 | GEO

XIST and MUC1-C form an autoregulatory pathway in driving cancer progression

Project description:MUC1-C /XIST autoregulatory axis is of importance in cancer progression where MUC1-C regulates XIST lncRNA levels in cancer

2024-12-04 | GSE263487 | GEO