scholarly journals CXXC finger protein 1-mediated histone H3 lysine-4 trimethylation is essential for proper meiotic crossover formation in mice

Development ◽  
2020 ◽  
Vol 147 (6) ◽  
pp. dev183764 ◽  
Author(s):  
Yu Jiang ◽  
Hui-Ying Zhang ◽  
Zhen Lin ◽  
Ye-Zhang Zhu ◽  
Chao Yu ◽  
...  
Keyword(s):  
Histone H3 ◽  
Finger Protein ◽  
Meiotic Crossover ◽  
Cxxc Finger Protein 1

scholarly journals Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes

2021 ◽  
Author(s):  
Qian-Qian Sha ◽  
Ye-Zhang Zhu ◽  
Yunlong Xiang ◽  
Jia-Li Yu ◽  
Xiao-Ying Fan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone H3 ◽  
Finger Protein ◽  
Maternal Genome ◽  
Wide Range ◽  
Transcriptional Changes ◽  
Nuclear Events ◽  
Genomic Regions ◽  
Cxxc Finger Protein 1

Abstract During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.

The epigenetic regulator Cfp1

2010 ◽  
Vol 1 (5-6) ◽  
pp. 325-334 ◽  
Author(s):  
David G. Skalnik
Keyword(s):  
Dna Methyltransferase ◽  
Cellular Differentiation ◽  
Cytosine Methylation ◽  
Cpg Islands ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Finger Protein ◽  
Epigenetic Regulator ◽  
Genomic Locations ◽  
Cxxc Finger Protein 1

AbstractNumerous epigenetic modifications have been identified and correlated with transcriptionally active euchromatin or repressed heterochromatin and many enzymes responsible for the addition and removal of these marks have been characterized. However, less is known regarding how these enzymes are regulated and targeted to appropriate genomic locations. Mammalian CXXC finger protein 1 is an epigenetic regulator that was originally identified as a protein that binds specifically to any DNA sequence containing an unmethylated CpG dinucleotide. Mouse embryos lacking CXXC finger protein 1 die prior to gastrulation, and embryonic stem cells lacking CXXC finger protein 1 are viable but are unable to achieve cellular differentiation and lineage commitment. CXXC finger protein 1 is a regulator of both cytosine and histone methylation. It physically interacts with DNA methyltransferase 1 and facilitates maintenance cytosine methylation. Rescue studies reveal that CXXC finger protein 1 contains redundant functional domains that are sufficient to support cellular differentiation and proper levels of cytosine methylation. CXXC finger protein 1 is also a component of the Setd1 histone H3-Lys4 methyltransferase complexes and functions to target these enzymes to unmethylated CpG islands. Depletion of CXXC finger protein 1 leads to loss of histone H3-Lys4 tri-methylation at CpG islands and inappropriate drifting of this euchromatin mark into areas of hetero-chromatin. Thus, one function of CXXC finger protein 1 is to serve as an effector protein that interprets cytosine methylation patterns and facilitates crosstalk with histone-modifying enzymes.

scholarly journals CXXC Finger Protein 1 Contains Redundant Functional Domains That Support Embryonic Stem Cell Cytosine Methylation, Histone Methylation, and Differentiation

2009 ◽  
Vol 29 (14) ◽  
pp. 3817-3831 ◽  
Author(s):  
Courtney M. Tate ◽  
Jeong-Heon Lee ◽  
David G. Skalnik
Keyword(s):  
Dna Binding ◽  
Point Mutation ◽  
Histone Methylation ◽  
Cytosine Methylation ◽  
Es Cells ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Functional Domains ◽  
Finger Protein ◽  
Cxxc Finger Protein 1

ABSTRACT CXXC finger protein 1 (Cfp1) is a regulator of both cytosine methylation and histone methylation. Murine embryonic stem (ES) cells lacking Cfp1 exhibit a decreased plating efficiency, decreased cytosine methylation, elevated global levels of histone H3-Lys4 trimethylation, and a failure to differentiate in vitro. Remarkably, transfection studies reveal that expression of either the amino half of Cfp1 (amino acids 1 to 367 [Cfp11-367]) or the carboxyl half of Cfp1 (Cfp1361-656) is sufficient to correct all of the defects observed with ES cells that lack Cfp1. However, a point mutation (C169A) that abolishes DNA-binding activity of Cfp1 ablates the rescue activity of the Cfp11-367 fragment, and a point mutation (C375A) that abolishes the interaction of Cfp1 with the Setd1 histone H3-Lys4 methyltransferase complexes ablates the rescue activity of the Cfp1361-656 fragment. Introduction of both the C169A and C375A point mutations ablates the rescue activity of the full-length Cfp1 protein. These results indicate that retention of either the Cfp1 DNA-binding domain or Setd1 interaction domain is required for Cfp1 rescue activity, and they illustrate the functional complexity of this critical epigenetic regulator. A model is presented for how epigenetic cross talk may explain the finding of redundant functional domains within Cfp1.

scholarly journals ERK2 phosphorylates the epigenetic regulator CXXC-finger protein 1 (CFP1)

2019 ◽  
Author(s):  
Aroon S. Karra ◽  
Aileen M. Klein ◽  
Svetlana Earnest ◽  
Steve Stippec ◽  
Chonlarat Wichaidit ◽  
...  
Keyword(s):  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Highly Active ◽  
Finger Protein ◽  
Extracellular Signal ◽  
Epigenetic Regulator ◽  
Mitogen Activated Protein ◽  
Cxxc Finger Protein 1

AbstractBackgroundThe Ras-Raf-MEK-ERK signaling pathway is essential for proper development and homeostatic regulation in eukaryotic cells and underlies progression of several types of cancer. Many pathway functions are performed by extracellular signal-regulated kinase (ERK)1 and 2 (ERK1/2), serine/threonine protein kinases of the mitogen-activated protein kinase (MAPK) family that interact with a large number of substrates and are highly active in the nucleus.ResultsWe identified the epigenetic regulator CXXC-finger protein 1 (CFP1) as a protein that interacts with ERK2 on chromatin. CFP1 is involved in multiple aspects of chromatin regulation, including histone methylation and DNA methylation. Here, we demonstrate the overlapping roles for ERK1/2 and CFP1 in regulation of immediate early gene (IEG) induction. Our work suggests multiple modes of co-regulation and demonstrates that CFP1 is required for an optimal signal-dependent response. We also show that CFP1 is an ERK2 substrate in vitro and identify several phosphorylation sites. Furthermore, we provide evidence that Su(var)3-9, Enhancer-of-zeste and Trithorax (Set)1b, a CFP1-interacting histone methylase, is phosphorylated by ERK2 and is regulated by CFP1.ConclusionOur work highlights ERK1/2 interactions with chromatin regulators that contribute to MAPK signaling diversity in the nucleus.

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