DNMTs and Impact of CpG Content, Transcription Factors, Consensus Motifs, lncRNAs, and Histone Marks on DNA Methylation

Loaeza-Loaeza, Jaqueline; Beltran, Adriana S.; Hernández-Sotelo, Daniel

doi:10.3390/genes11111336

Cited by 43 publications

(22 citation statements)

References 126 publications

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“…It plays a major role in a variety of biological and molecular processes during embryonic development including X-chromosome inactivation, genomic imprinting, transcription, chromatin organization and chromosome stability [1-3 � ]. 5mC is established by the DNA methyltransferases (DNMTs) [1,2,4] and removed either catalytically by the Ten Eleven Translocation (TET) proteins or passively by dilution over cellular divisions in absence of maintenance [5,6].…”

Section: -Methylcytosine (Or 5mcmentioning

confidence: 99%

The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome

et al. 2021

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Ten-Eleven Translocation (TET) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) leading to a dynamic epigenetic state of DNA that can influence transcription and chromatin organization. While TET proteins interact with complexes involved in transcriptional repression and activation, the overall understanding of the molecular mechanisms involved in TET-mediated regulation of gene expression still remains limited. Here, we show that TET proteins interact with the chromatin remodelling protein lymphoid-specific helicase (LSH/HELLS) in vivo and in vitro. In mouse embryonic fibroblasts (MEFs) and embryonic stem cells (ESCs) knock out of Lsh leads to a significant reduction of 5-hydroxymethylation amount in the DNA. Whole genome sequencing of 5hmC in wild-type versus Lsh knock-out MEFs and ESCs showed that in absence of Lsh, some regions of the genome gain 5hmC while others lose it, with mild correlation with gene expression changes. We further show that differentially hydroxymethylated regions did not completely overlap with differentially methylated regions indicating that changes in 5hmC distribution upon Lsh knock-out are not a direct consequence of 5mC decrease. Altogether, our results suggest that LSH, which interacts with TET proteins, contributes to the regulation of 5hmC levels and distribution in MEFs and ESCs.

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Section: -Methylcytosine (Or 5mcmentioning

confidence: 99%

The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome

et al. 2021

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“…DNMT3 plays a central role in epigenetic modifications of the genome via DNA methylation [ 84 ]. Barrès and colleagues showed that, in skeletal muscle from patients with T2DM, DNMT3-related non-CpG hypermethylation occurred in the PGC-1α promoter, which resulted in decreased PGC-1α gene expression and mtDNA levels [ 85 ].…”

Section: Mitochondria and Pgc-1α In Wat During Obesity Or Crmentioning

confidence: 99%

Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

Kobayashi

Deguchi

Nozaki

et al. 2021

IJMS

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Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) regulates mitochondrial DNA replication and mitochondrial gene expression by interacting with several transcription factors. White adipose tissue (WAT) mainly comprises adipocytes that store triglycerides as an energy resource and secrete adipokines. The characteristics of WAT vary in response to systemic and chronic metabolic alterations, including obesity or caloric restriction. Despite a small amount of mitochondria in white adipocytes, accumulated evidence suggests that mitochondria are strongly related to adipocyte-specific functions, such as adipogenesis and lipogenesis, as well as oxidative metabolism for energy supply. Therefore, PGC-1α is expected to play an important role in WAT. In this review, we provide an overview of the involvement of mitochondria and PGC-1α with obesity- and caloric restriction-related physiological changes in adipocytes and WAT.

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“…For instance, TETs loss of function is associated with genome wide hypomethylation [ 7 ]. DNA methylation is initiated by a special histone marks pattern, by proteins that bind methylated DNA, by tissue-specific transcription factors [ 8 ]. Several studies have revealed many transcription factors that can interact with DNMT1 and DNMT3a/3b DNA methyltransferases [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Kaiso Regulates DNA Methylation Homeostasis

Kaplun

Starshin

Sharko

et al. 2021

IJMS

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Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NCoR, SMRT repressive complexes affecting histone modifications. On the other hand, the deficiency of Kaiso resulted in reduced methylation of ICR in H19/Igf2 locus and Oct4 promoter in mouse embryonic fibroblasts. However, nothing is known about how Kaiso influences DNA methylation at the genome level. Here we show that deficiency of Kaiso led to whole-genome hypermethylation, using Kaiso deficient human renal cancer cell line obtained via CRISPR/CAS9 genome editing. However, Kaiso serves to protect genic regions, enhancers, and regions with a low level of histone modifications from demethylation. We detected hypomethylation of binding sites for Oct4 and Nanog in Kaiso deficient cells. Kaiso immunoprecipitated with de novo DNA methyltransferases DNMT3a/3b, but not with maintenance methyltransferase DNMT1. Thus, Kaiso may attract methyltransferases to surrounding regions and modulate genome methylation in renal cancer cells apart from being methyl DNA binding protein.

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DNMTs and Impact of CpG Content, Transcription Factors, Consensus Motifs, lncRNAs, and Histone Marks on DNA Methylation

Cited by 43 publications

References 126 publications

The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome

The chromatin remodelling protein LSH/HELLS regulates the amount and distribution of DNA hydroxymethylation in the genome

Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

Kaiso Regulates DNA Methylation Homeostasis

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