5-methylcytosine is found in the context of paired symmetrical methylation of a CpG site. In normal somatic cells, most CpG sites are heavily methylated, while CpG islands (sites of CpG clusters) in germ-line tissues and located near promoters, remain unmethylated thus allowing gene expression to occur. When a CpG island in the promoter region of a gene is methylated, expression of the gene is repressed. The addition of methyl groups is controlled at several different levels in cells and is carried out by a family of enzymes called DNA methyltransferases (DNMTs).
Three DNMTs are required for establishment and maintenance of DNA methylation patterns. DNMT1 is responsible for the maintenance of DNA methylation patterns, while DNMT3a and 3b mediate establishment of new or de novo DNA methylation patterns. Even with this knowledge about DNMT function, questions still remain about how DNA methylation is altered.
Researchers at Harvard Stem Cell Institute, Beth Israel Deaconess Medical Center and Universita Cattolica del Sacro Cuore-Institute of Hematology, along with other collaborators sought to address this question by examining how transcription may be involved in regulating DNA methylation. In particular, they investigated the dynamics between DNMT1 and non-coding RNAs using the methylation sensitive gene CEBPA.
Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but are not translated into proteins. In general ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Many long non-coding RNAs (lncRNAs) can complex with chromatin-modifying proteins and recruit their catalytic activity to specific sites in the genome, thereby modifying chromatin states and influencing gene expression.
The authors identified a functional ncRNA transcribed from the CEBPA locus, ecCEBPA (extra coding CEBPA), which regulates CEBPA methylation by interacting with DNMT1 thus preventing CEBPA gene methylation.
Their findings are summarized below:
Source: Read more about their findings and get all of the details here: Di Ruscio A., Ebralidze AK., et al, DNMT1-interacting RNAs Block Gene-Specific DNA Methylation, Nature (2013, Oct 9).
References: [1] Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [3] Università Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy [4].
Understanding trait inheritance is crucial for unraveling the complexities of life's blueprint and how it…
Flame retardants are ubiquitous chemicals added to numerous consumer products to prevent the spread of…
Alzheimer's disease is a degenerative brain disorder that impacts millions globally. While the exact cause…
In the quest to understand the intricate interplay between genetics and the environment in disease…
Cleft lip and palate stand out as the most prevalent craniofacial birth anomalies worldwide, affecting…
In the quest to unravel the mysteries of aging, scientists have long turned to our…