Evolutionarily conserved enhancer-associated features within the MYEOV locus suggest a regulatory role for this non-coding DNA region in cancer

Sep 21, 2026

Uploaded by Liam

The myeloma overexpressed gene (MYEOV) has been proposed as a proto-oncogene because elevated RNA transcript levels occur across multiple cancers, yet functional evidence for a MYEOV protein is lacking. This study tests whether MYEOV acts as an enhancer regulating CCND1 and LTO1. Using ATAC-STARR-seq, enhancer histone marks, 3D genome interaction datasets, and comparative sequence/homology analyses, the work identifies evolutionarily conserved, enhancer-like states at a MYEOV 3′ element, including primate orthologues and mouse enhancer homolog interactions with Ccnd1. Findings support a primate-specific MYEOV de novo ORF arising from an older conserved enhancer region, enabling non-primate model studies of MYEOV regulation in cancer.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

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Introduction

Background on MYEOV and its proposed proto-oncogenic role

TYPE Original Research PUBLISHED 30 July 2024 DOI 10.3389/fcell.2024.1294510 OPEN ACCESS EDITED BY Serena Ghisletti, European Institute of Oncology (IEO), Italy REVIEWED BY Jose Bessa, Universidade do Porto, Portugal Tianyun Long, University of California, San Diego, United States *CORRESPONDENCE Daniel Rico, [daniel.rico@cabimer.es](daniel.rico@cabimer.es)[ ](daniel.rico@cabimer.es)Lisa J. Russell, [lisa.russell@newcastle.ac.uk](lisa.russell@newcastle.ac.uk)[ ](lisa.russell@newcastle.ac.uk)†These authors share ﬁrst authorship RECEIVED 14 September 2023 ACCEPTED 01 July 2024 PUBLISHED 30 July 2024 CITATION Davidson BSA, Arcila-Galvis JE, Trevisan-Herraz M, Mikulasova A, Brackley CA, Russell LJ and Rico D (2024), Evolutionarily conserved enhancer-associated features within the MYEOV locus suggest a regulatory role for this non-coding DNA region in cancer. Front. Cell Dev. Biol. 12:1294510 . doi: 10.3389/fcell.2024.1294510 COPYRIGHT © 2024 Davidson, Arcila-Galvis, TrevisanHerraz, Mikulasova, Brackley, Russell and Rico. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Evolutionarily conserved enhancer-associated features within the MYEOV locus suggest a regulatory role for this non-coding DNA region in cancer Brigid S. A. Davidson 1†, Juliana Estefania Arcila-Galvis 1†, Marco Trevisan-Herraz 1, Aneta Mikulasova 1, Chris A. Brackley 2, Lisa J. Russell 1* and Daniel Rico 1,3* 1Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom, 2SUPA, School of Physics and Astronomy, University of Edinburgh, Edinburgh, United Kingdom, 3CABIMER, CSICUniversidad de Sevilla-Universidad Pablo de Olavide-Junta de Andalucía, Seville, Spain The myeloma overexpressed gene (MYEOV) has been proposed to be a protooncogene due to high RNA transcript levels found in multiple cancers, including myeloma, breast, lung, pancreas and esophageal cancer. The presence of an open reading frame (ORF) in humans and other primates suggests protein-coding potential. Yet, we still lack evidence of a functional MYEOV protein. It remains undetermined how MYEOV overexpression affects cancerous tissues. In this work, we show that MYEOV has likely originated and may still function as an enhancer, regulating CCND1 and LTO1 . Firstly, MYEOV 3′ enhancer activity was conﬁrmed in humans using publicly available ATAC-STARR-seq data, performed on B-cell-derived GM12878 cells. We detected enhancer histone marks H3K4me1 and H3K27ac overlapping MYEOV in multiple healthy human tissues, which include B cells, liver and lung tissue. The analysis of 3D genome datasets revealed chromatin interactions between a MYEOV-3′ -putative enhancerand the proto-oncogene CCND1 . BLAST searches and multi-sequence alignment results showed that DNA sequence from this human enhancer element is conserved from the amphibians/amniotes divergence, with a 273 bp conserved region also found in all mammals, and even in chickens, where it is consistently located near the corresponding CCND1 orthologues. Furthermore, we observed conservation of an active enhancer state in the MYEOV orthologues of four non-human primates, dogs, rats, and mice. When studying this homologous region in mice, where the ORF of MYEOV is absent, we not only observed an enhancer chromatin state but also found interactions between the mouse enhancer homolog and Ccnd1 using 3D-genome interaction data. This is similar to the interaction observed in humans and, interestingly, coincides with CTCF binding sites in both species. Taken together, this suggests that MYEOV is

FAQs

What is the main functional question addressed about MYEOV in this study?

The study investigates whether MYEOV overexpression in cancer tissues can be explained by a regulatory role, despite missing evidence for a functional MYEOV protein.

How do the authors assess whether MYEOV behaves like an enhancer?

They confirm MYEOV 3′ enhancer activity using publicly available ATAC-STARR-seq data and detect enhancer histone marks overlapping MYEOV in multiple healthy human tissues.

What evidence supports evolutionary conservation of the MYEOV regulatory element?

Comparative sequence and BLAST/multi-sequence alignment results reveal a 273 bp conserved region across mammals (and also located near CCND1 orthologues in chickens), while enhancer states are observed in MYEOV orthologues across multiple non-human primates.

Sep 21, 2026

Uploaded by Liam