Biology

Discovery of genes required for body axis and limb formation by global identification of retinoic acid–regulated epigenetic marks


by Marie Berenguer, Karolin F. Meyer, Jun Yin, Gregg Duester

Identification of target genes that mediate required functions downstream of transcription factors is hampered by the large number of genes whose expression changes when the factor is removed from a specific tissue and the numerous binding sites for the factor in the genome. Retinoic acid (RA) regulates transcription via RA receptors bound to RA response elements (RAREs) of which there are thousands in vertebrate genomes. Here, we combined chromatin immunoprecipitation sequencing (ChIP-seq) for epigenetic marks and RNA-seq on trunk tissue from wild-type and Aldh1a2-/- embryos lacking RA synthesis that exhibit body axis and forelimb defects. We identified a relatively small number of genes with altered expression when RA is missing that also have nearby RA-regulated deposition of histone H3 K27 acetylation (H3K27ac) (gene activation mark) or histone H3 K27 trimethylation (H3K27me3) (gene repression mark) associated with conserved RAREs, suggesting these genes function downstream of RA. RA-regulated epigenetic marks were identified near RA target genes already known to be required for body axis and limb formation, thus validating our approach; plus, many other candidate RA target genes were found. Nuclear receptor 2f1 (Nr2f1) and nuclear receptor 2f2 (Nr2f2) in addition to Meis homeobox 1 (Meis1) and Meis homeobox 2 (Meis2) gene family members were identified by our approach, and double knockouts of each family demonstrated previously unknown requirements for body axis and/or limb formation. A similar epigenetic approach can be used to determine the target genes for any transcriptional regulator for which a knockout is available.

Source link

WordPress database error: [Error writing file '/tmp/MYc4DRc4' (Errcode: 28 - No space left on device)]
SELECT SQL_CALC_FOUND_ROWS wp_posts.ID FROM wp_posts LEFT JOIN wp_term_relationships ON (wp_posts.ID = wp_term_relationships.object_id) WHERE 1=1 AND wp_posts.ID NOT IN (371210) AND ( wp_term_relationships.term_taxonomy_id IN (32) ) AND wp_posts.post_type = 'post' AND (wp_posts.post_status = 'publish') GROUP BY wp_posts.ID ORDER BY RAND() LIMIT 0, 3

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy

COVID-19

COVID-19 (Coronavirus) is a new illness that is having a major effect on all businesses globally LIVE COVID-19 STATISTICS FOR World