The role of DOT1L in regulating bidirectional expression of mRNA-lncRNA pairs in developing brain

CHUNG WY; VILLARREAL A; VOGEL T

Freiburg

Congreso; 3rd German-Catalan Workshop on Epigenetic and Disease; 2016

CRC992: Medical Epigenetics-From basic mechanisms to clinical applications.

DOT1 L methylates the lysine residue (K) exclusively and specifically on position 79 of histone 3(H3) toregulate transcription of crucial genes during brain development. ln E14.5 mouse dorsaltelencephalons, we find that there is a cluster of 64 bidirectional mRNA-lncRNA pairs predominatelymark with H3K79me2 from their transcription start site (TSS) to the end site (TES). From the RNAsequencing , 24 of these pairs have significantly altered expression in the conditional DOT1 L knockoutcerebrum. We further validate 2 novel pairs, Satb2 - 9130024F11Rik and Slc32a1 - Gm1 4204, anddelineate their positive correlated expression pattern, to each other and DOT1L, in neural linage.Taken together, our data suggests a potential role of DOT1 L in coordinating the expression of thesemRNA-lncRNA pairs via acting on bidirectional promoters, providing insight to uncover regulatorypathways essential for proper brain development.