Differential DNA methylation and CTCF binding between the ESR1 promoter a of MCF-7 and MDA-MB-231 breast cancer cells

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

ESR1 is expressed by 60–70% of breast tumours. it’s a good prognosis factor and the target of hormone therapy. Optimization of ESR1 reactivation therapy is currently ongoing. Here we probe if the transcription factor CTCF plays a role in the differential expression of ESR1 in the breast cancer cell lines MCF-7 (ESR1+) and MDA-MB-231 (ESR1-).

Methods and results

Knockdown of CTCF in MCF-7 resulted in decreased ESR1 gene expression. CTCF binds to the promoter of ESR1 in MCF-7 but not in MDA-MB-231 cells. CTCF ESR1 binding sites are unmethylated in MCF7 but methylated in MDA-MB-231 cells.

Conclusion

ESR1 expression in MCF7 cells is dependent on CTCF expression. CTCF can bind to specific regions of the promotor of ESR1 gene in MCF-7 cells but not in MDA-MB-231 cells, this correlates with the methylation status of these regions and could be involved in the transcriptional regulation of ESR1.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11033-023-09171-0.

Related collections

Most cited references 10

Record: found
Abstract: found
Article: found

Is Open Access

An Integrated Encyclopedia of DNA Elements in the Human Genome

Iakes Ezkurdia (2016)

Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research.

0 comments Cited 3226 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.

Tae Hoon Kim, Ziedulla K Abdullaev, Andrew D. M. Smith … (2007)

Insulator elements affect gene expression by preventing the spread of heterochromatin and restricting transcriptional enhancers from activation of unrelated promoters. In vertebrates, insulator's function requires association with the CCCTC-binding factor (CTCF), a protein that recognizes long and diverse nucleotide sequences. While insulators are critical in gene regulation, only a few have been reported. Here, we describe 13,804 CTCF-binding sites in potential insulators of the human genome, discovered experimentally in primary human fibroblasts. Most of these sequences are located far from the transcriptional start sites, with their distribution strongly correlated with genes. The majority of them fit to a consensus motif highly conserved and suitable for predicting possible insulators driven by CTCF in other vertebrate genomes. In addition, CTCF localization is largely invariant across different cell types. Our results provide a resource for investigating insulator function and possible other general and evolutionarily conserved activities of CTCF sites.

0 comments Cited 373 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Genome-wide identification of in vivo protein–DNA binding sites from ChIP-Seq data

Raja Jothi, Suresh Cuddapah, Artem Barski … (2008)

ChIP-Seq, which combines chromatin immunoprecipitation (ChIP) with ultra high-throughput massively parallel sequencing, is increasingly being used for mapping protein–DNA interactions in-vivo on a genome scale. Typically, short sequence reads from ChIP-Seq are mapped to a reference genome for further analysis. Although genomic regions enriched with mapped reads could be inferred as approximate binding regions, short read lengths (∼25–50 nt) pose challenges for determining the exact binding sites within these regions. Here, we present SISSRs (Site Identification from Short Sequence Reads), a novel algorithm for precise identification of binding sites from short reads generated from ChIP-Seq experiments. The sensitivity and specificity of SISSRs are demonstrated by applying it on ChIP-Seq data for three widely studied and well-characterized human transcription factors: CTCF (CCCTC-binding factor), NRSF (neuron-restrictive silencer factor) and STAT1 (signal transducer and activator of transcription protein 1). We identified 26 814, 5813 and 73 956 binding sites for CTCF, NRSF and STAT1 proteins, respectively, which is 32, 299 and 78% more than that inferred previously for the respective proteins. Motif analysis revealed that an overwhelming majority of the identified binding sites contained the previously established consensus binding sequence for the respective proteins, thus attesting for SISSRs’ accuracy. SISSRs’ sensitivity and precision facilitated further analyses of ChIP-Seq data revealing interesting insights, which we believe will serve as guidance for designing ChIP-Seq experiments to map in vivo protein–DNA interactions. We also show that tag densities at the binding sites are a good indicator of protein–DNA binding affinity, which could be used to distinguish and characterize strong and weak binding sites. Using tag density as an indicator of DNA-binding affinity, we have identified core residues within the NRSF and CTCF binding sites that are critical for a stronger DNA binding.

0 comments Cited 224 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Alejandro Zentella-Dehesa:

ORCID: http://orcid.org/0000-0002-5595-1466

azentell@iibiomedicas.unam.mx

Journal

Journal ID (nlm-ta): Mol Biol Rep

Journal ID (iso-abbrev): Mol Biol Rep

Title: Molecular Biology Reports

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 0301-4851

ISSN (Electronic): 1573-4978

Publication date (Electronic): 18 January 2024

Publication date PMC-release: 18 January 2024

Publication date (Print): 2024

Volume: 51

Issue: 1

Electronic Location Identifier: 148

Affiliations

[1 ]Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, ( https://ror.org/01tmp8f25) Ciudad de México, 04510 México

[2 ]Programa de Investigación en Cáncer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, ( https://ror.org/01tmp8f25) Ciudad de México, 04510 Mexico

[3 ]Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, ( https://ror.org/00xgvev73) Ciudad de México, 14080 México

[4 ]GRID grid.419167.c, ISNI 0000 0004 1777 1207, División de Investigación Básica, Laboratorio de Virus y Cancer, Secretaría de Salud, , Instituto Nacional de Cancerología, ; Ciudad de México, 14080 México

[5 ]Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, ( https://ror.org/01tmp8f25) Ciudad de México, 04510 México

[6 ]Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, ( https://ror.org/01tmp8f25) Ciudad de México, 04510 México

[7 ]GRID grid.419216.9, ISNI 0000 0004 1773 4473, Laboratorio de Oncología Experimental, Secretaría de Salud, , Instituto Nacional de Pediatría, ; Ciudad de México, 04530 México

[8 ]Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México‑Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, ( https://ror.org/00xgvev73) Ciudad de México, 14080 México

[9 ]GRID grid.413678.f, Cancer Center, , American British Cowdray Medical Center, ; Ciudad de México, 01120 Mexico

Author information

Alejandro Zentella-Dehesa http://orcid.org/0000-0002-5595-1466

Article

Publisher ID: 9171

DOI: 10.1007/s11033-023-09171-0

PMC ID: 10796618

PubMed ID: 38236307

SO-VID: 79ff4289-dabe-4e34-874b-6fd9f4dc3859

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 May 2023

Date accepted : 15 December 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003141, Consejo Nacional de Ciencia y Tecnología;

Award ID: 172558

Custom metadata

ScienceOpen disciplines: Molecular biology

Keywords: ctcf,esr1,tnbc,dna methylation,breast cancer

Data availability:

ScienceOpen disciplines: Molecular biology

Keywords: ctcf, esr1, tnbc, dna methylation, breast cancer

Differential DNA methylation and CTCF binding between the ESR1 promoter a of MCF-7 and MDA-MB-231 breast cancer cells

Read this article at

Abstract

Background

Methods and results

Conclusion

Supplementary Information

Related collections

Higher order chromatin architecture

Most cited references 10

An Integrated Encyclopedia of DNA Elements in the Human Genome

Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.

Genome-wide identification of in vivo protein–DNA binding sites from ChIP-Seq data

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 493

Most referenced authors 480