Transcription Factors Involved in DNA Demethylation During Human Cellular Development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA720888 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNA methylation is an important epigenetic modification involved in the regulation of mammalian gene expression, with each type of cell developing a specific methylation profile during its differentiation. The enzymatic mechanisms of DNA methylation and demethylation are well understood; however, little is known about how cell-type-specific DNA methylation profiles are developed. Recently, a small subgroup of transcription factors (TFs) have been shown to promote DNA demethylation at their binding sites (e.g., RUNX1 reported by our group).
2022-03-30 | GSE171773 | GEO
Project description:DNA methylation of CpG dinucleotides is an important epigenetic modification involved in the regulation of mammalian gene expression, with each type of cell developing a specific methylation profile during its differentiation. Recently, it has been shown that a small subgroup of transcription factors (TFs) might promote DNA demethylation at their binding sites. We developed a bioinformatics pipeline to predict from genome-wide DNA methylation data TFs that promote DNA demethylation at their binding site. We applied the pipeline to International Human Epigenome Consortium methylome data and selected 393 candidate transcription factor binding motifs and associated 383 TFs that are likely associated with DNA demethylation. Validation of a subset of the candidate TFs using an in vitro assay suggested that 28 of 49 TFs from various TF families had DNA-demethylation-promoting activity; TF families, such as bHLH and ETS, contained both TFs with and without the activity. The identified TFs showed large demethylated/methylated CpG ratios and their demethylated CpGs showed significant bias toward hypermethylation in original cells. Furthermore, the identified TFs promoted demethylation of distinct sets of CpGs, with slight overlap of the targeted CpGs among TF family members, which was consistent with the results of a gene ontology (GO) term analysis of the identified TFs. Gene expression analysis of the identified TFs revealed that multiple TFs from various families are specifically expressed in human cells and tissues. Together, our results suggest that a large number of TFs from various TF families are associated with cell-type-specific DNA demethylation during human cellular development.
| S-EPMC8942926 | biostudies-literature
Project description:Background: DNA methylation is a fundamental epigenetic modification which is involved in many biological systems such as differentiation and disease. We and other groups recently discovered that a part of transcription factors (TFs) plays a role for site-specificity determination of DNA demethylation in a binding site-directed manner, although number of reports for such TFs are limited. Results: Here, we develop a screening system to identify TFs which induce the binding site-directed DNA methylation changes. The system consists of ectopic expression of target TFs in model cells and the DNA methylome analysis followed by overrepresentation analysis of the corresponding TF binding motif at differentially methylated regions. Our system successfully identifies binding site-directed demethylation of SPI1 which is known to promote DNA demethylation in a binding-site directed manner. We extend our screening system to 15 master TFs which are involved in cellular differentiations, and identified 8 (RUNX3, GATA2, CEBPB, MAFB, NR4A2, MYOD1, CEBPA and TBX5) novel binding site-directed DNA demethylation inducing TFs. Gene ontology and specifically expressing tissue enrichment analysis revealed that those 8 TFs demethylate genome regions which are associated with corresponding biological roles, supporting performance of our system. We also describe characteristics of the binding site-directed DNA demethylation induced by those TFs; targeting highly methylated CpGs, local DNA demethylation, and overlap of demethylated regions between same family TFs. Conclusion: Thus, our results emphasize usefulness of the developed screening system for identification of TFs which induce DNA demethylation in a site-directed manner.
2017-11-29 | GSE102822 | GEO
Project description:DNA methylation is a major epigenetic modification for gene silencing and is dramatically altered spatiotemporally during cellular development. However, the roles of DNA methylation dynamics and regulation in cellular development remain unclear. The present analyses of DNA methylome dynamics during hematopoietic development suggest that DNA demethylation pre-defines the gene expression potential of terminal differentiation-specific genes at the progenitor cell stage and is regulated by lineage-specific transcription factors (TFs). Demethylation of majority of hypo-methylated CpGs in terminally differentiated cells occurs during the progenitor cell stage and is associated with rapid upregulation of terminal differentiation-specific genes. Accordingly, TF overrepresentation analyses indicated that lineage-specific TFs regulate DNA demethylation. The present experiments show that RUNX1 induces site-directed active DNA demethylation by recruiting DNA demethylation enzymes. Collectively, the present data indicate an integrated system of DNA methylation and gene expression during cellular development.
2017-08-10 | GSE85523 | GEO
Project description:Genomic factors involved in chromosome rearrangements
| PRJNA268998 | ENA
Project description:DNA methylation is a major epigenetic modification for gene silencing and is dramatically altered spatiotemporally during cellular development. However, the roles of DNA methylation dynamics and regulation in cellular development remain unclear. The present analyses of DNA methylome dynamics during hematopoietic development suggest that DNA demethylation pre-defines the gene expression potential of terminal differentiation-specific genes at the progenitor cell stage and is regulated by lineage-specific transcription factors (TFs). Demethylation of majority of hypo-methylated CpGs in terminally differentiated cells occurs during the progenitor cell stage and is associated with rapid upregulation of terminal differentiation-specific genes. Accordingly, TF overrepresentation analyses indicated that lineage-specific TFs regulate DNA demethylation. The present experiments show that RUNX1 induces site-directed active DNA demethylation by recruiting DNA demethylation enzymes. Collectively, the present data indicate an integrated system of DNA methylation and gene expression during cellular development.
2017-08-10 | GSE85524 | GEO
Project description:Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate
| PRJNA401421 | ENA
Project description:Secretome from Leptospira interrogans and Host Cells during Infection: Leptospiral Virulence Factors and Cellular Proteins Involved in Stress and Inflammation
2020-05-24 | PXD019375 |
Project description:Factors involved in the mouse molar development assessed using RNA-Seq
| PRJEB74655 | ENA
Project description:Gall formation on the belowground parts of plants infected with Plasmodiophora brassicae is the result of extensive host cellular reprogramming. The development of these structures is a consequence of increased cell proliferation followed by massive enlargement of cells colonised with the pathogen. Drastic changes in cellular growth patterns create local deformities in the roots and hypocotyl giving rise to mechanical tensions within the tissue of these organs. Host cell wall extensibility and recomposition accompanies growth of the gall, influences pathogen spread and also pathogen life cycle progression. Demethylation of pectin within the extracellular matrix may play an important role in P. brassicae-driven hypertrophy of host underground organs. Through proteomic analysis of the cell wall we identified proteins accumulating in the galls developing on the underground parts of Arabidopsis thaliana plants infected with P. brassicae. One of the key proteins identified was the pectin methylesterase PME18; we further characterised its expression and conducted functional and anatomic studies in the knock-out mutant and used Raman spectroscopy to study the status of pectin in P. brassicae infected galls. We found that late stages of gall formation are accompanied with increased levels of Pectin Methylesterase 18 (PME18). We have also shown, that the massive enlargement of cells colonised with P. brassicae coincides with decreases in pectin methylation. In pme18-1 knock-out mutants P. brassicae could still induce demethylation; however, the galls in this line were smaller and cellular expansion was less pronounced. Alteration in pectin demethylation in the host resulted in changes in pathogen distribution and slowed down disease progression. To conclude, P. brassicae driven host organ hypertrophy observed during clubroot disease is accompanied by pectin demethylation in the extracellular matrix. The pathogen hijacks endogenous host mechanisms involved in cell wall loosening to create an optimal cellular environment for completion of its life cycle and eventual release of resting spores facilitated by degradation of demethylated pectin polymers.
2021-07-20 | PXD026660 | Pride