Increasing evidence has shown that many long non-coding RNAs (lncRNAs) are involved in gene regulation in a variety of ways such as transcriptional, post-transcriptional and epigenetic regulation. Promoter-associated non-coding RNAs (pancRNAs), which are categorized into the most abundant single-copy lncRNA biotype, play vital regulatory roles in finely tuning cellular specification at the epigenomic level. In short, pancRNAs can directly or indirectly regulate downstream genes to participate in the development of organisms in a cell-specific manner. In this review, we will introduce the evolutionarily acquired characteristics of pancRNAs as determined by comparative epigenomics and elaborate on the research progress on pancRNA-involving processes in mammalian embryonic development, including neural differentiation.