A study published in Nature (2016) investigated the local regulation of gene expression by long noncoding RNAs (lncRNAs) and their promoters. The research focused on 12 lncRNA loci and 6 protein-coding gene loci in mouse embryonic stem cells (mESCs). The findings revealed that 5 of the lncRNA loci influence the expression of neighboring genes in cis, and these effects do not require the specific lncRNA transcripts but rather general processes associated with their production, including enhancer-like activity of gene promoters, transcription, and splicing. Similarly, 4 of 6 protein-coding loci also influenced the expression of neighboring genes, indicating that both noncoding and coding loci can directly influence local gene expression. The study used genetic manipulations to delete promoters and analyze the effects on gene expression. It found that promoter deletions significantly affected the expression of nearby genes in an allele-specific manner. The effects were not limited to lncRNA loci, as protein-coding genes also showed similar regulatory effects. The results suggest that 'crosstalk' among neighboring genes is a prevalent phenomenon that can involve multiple mechanisms, including enhancer-like functions of promoters, transcription, and splicing. The study also identified that the 5' splice site and the process of transcription in the Blustr locus are important for its ability to regulate Sfmbt2. This indicates that the Blustr RNA is required for Sfmbt2 activation, although this mechanism does not appear to depend on the precise sequence of the RNA beyond the presence of initial splice signals. The findings suggest that the local effects of lncRNAs may be mediated by DNA regulatory elements in promoters, and that these mechanisms may contribute to the function and evolution of some genomic loci that produce lncRNAs. The study also found that the frequent 'crosstalk' between neighboring genes indicates that gene loci can encode multiple independent categories of functions. Category I involves functions of the RNA product, while Category II involves the effects of transcription-related processes on the regulation of other nearby genes. The study highlights the importance of cis regulatory connections between neighboring genes in both protein-coding and noncoding loci, suggesting that these connections represent a fundamental property of mammalian gene regulatory networks. The properties of these cis regulatory connections, including mechanisms for specificity and the potential for cooperative dynamics of gene activation, represent key areas for future investigation.A study published in Nature (2016) investigated the local regulation of gene expression by long noncoding RNAs (lncRNAs) and their promoters. The research focused on 12 lncRNA loci and 6 protein-coding gene loci in mouse embryonic stem cells (mESCs). The findings revealed that 5 of the lncRNA loci influence the expression of neighboring genes in cis, and these effects do not require the specific lncRNA transcripts but rather general processes associated with their production, including enhancer-like activity of gene promoters, transcription, and splicing. Similarly, 4 of 6 protein-coding loci also influenced the expression of neighboring genes, indicating that both noncoding and coding loci can directly influence local gene expression. The study used genetic manipulations to delete promoters and analyze the effects on gene expression. It found that promoter deletions significantly affected the expression of nearby genes in an allele-specific manner. The effects were not limited to lncRNA loci, as protein-coding genes also showed similar regulatory effects. The results suggest that 'crosstalk' among neighboring genes is a prevalent phenomenon that can involve multiple mechanisms, including enhancer-like functions of promoters, transcription, and splicing. The study also identified that the 5' splice site and the process of transcription in the Blustr locus are important for its ability to regulate Sfmbt2. This indicates that the Blustr RNA is required for Sfmbt2 activation, although this mechanism does not appear to depend on the precise sequence of the RNA beyond the presence of initial splice signals. The findings suggest that the local effects of lncRNAs may be mediated by DNA regulatory elements in promoters, and that these mechanisms may contribute to the function and evolution of some genomic loci that produce lncRNAs. The study also found that the frequent 'crosstalk' between neighboring genes indicates that gene loci can encode multiple independent categories of functions. Category I involves functions of the RNA product, while Category II involves the effects of transcription-related processes on the regulation of other nearby genes. The study highlights the importance of cis regulatory connections between neighboring genes in both protein-coding and noncoding loci, suggesting that these connections represent a fundamental property of mammalian gene regulatory networks. The properties of these cis regulatory connections, including mechanisms for specificity and the potential for cooperative dynamics of gene activation, represent key areas for future investigation.