{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EVX1‐AS is a long non‐coding RNA transcribed in a divergent orientation relative to the homeotic transcription factor gene EVX1. Its expression is tightly coordinated with that of EVX1 during key developmental stages, particularly in mesendoderm specification. In one study, genetic deletions affecting the shared promoter of EVX1 and EVX1‐AS produced patterning defects identical to those seen with disruption of the EVX1 DNA‐binding domain, indicating that EVX1‐AS does not have an independent, trans‐acting function but likely modulates EVX1 expression in cis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, genome-wide analysis of divergent long noncoding RNAs has shown that EVX1‐AS can promote the transcription of its neighboring EVX1 gene—its early, broad expression preceding a rapid and robust induction of EVX1 supports its role as an upstream facilitator of mesendodermal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Furthermore, chromatin immunoprecipitation studies during embryonic stem cell differentiation have demonstrated that EVX1‐AS is associated with active chromatin marks (such as H3K4me3) and components of the histone methyltransferase complex (MLL1), suggesting that it may help shape the local epigenetic landscape to ensure proper activation of homeotic loci."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies point to a model in which EVX1‐AS functions as a cis‐regulatory noncoding RNA that fine-tunes EVX1 expression during embryonic development. Although its mechanistic contributions—as a facilitator of chromatin modification and transcriptional activation—appear critical for proper mesendodermal patterning, its role seems inseparable from that of its linked coding gene, underscoring the complexity of intertwined regulatory networks during early development.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Charles C Bell, Paulo P Amaral, Anton Kalsbeek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Evx1/Evx1as gene locus regulates anterior-posterior patterning during gastrulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep26657"}], "href": "https://doi.org/10.1038/srep26657"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27226347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27226347"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sai Luo, J Yuyang Lu, Lichao Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2016.01.024"}], "href": "https://doi.org/10.1016/j.stem.2016.01.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26996597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26996597"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marcel E Dinger, Paulo P Amaral, Tim R Mercer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gr.078378.108"}], "href": "https://doi.org/10.1101/gr.078378.108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18562676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18562676"}]}]}]}