PT - JOURNAL ARTICLE AU - Michael Costallat AU - Christophe Rachez AU - Christian Muchardt TI - Alu repeats at the boundaries of regulatory elements shape the epigenetic environment of immune genes in T cells AID - 10.1101/2021.11.21.469436 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.21.469436 4099 - http://biorxiv.org/content/early/2021/11/21/2021.11.21.469436.short 4100 - http://biorxiv.org/content/early/2021/11/21/2021.11.21.469436.full AB - Promoters and enhancers are sites of transcription initiation (TSSs) and carry active histone modifications, including H3K4me1, H3K4me3, and H3K27ac. Yet, the principles governing the boundaries of such regulatory elements are still poorly characterized. Alu elements are good candidates for a boundary function, being highly abundant in gene-rich regions, while essentially excluded from regulatory elements. Here, we show that the interval from the TSS to the first upstream Alu accommodates essentially all H3K4me3 marks, while excluding DNA methylation. In contrast, enhancer-enriched H3K4me1 and H3K27ac marks eventually cross the first-Alu limit, consistent with enhancer-annotation occasionally overlapping with Alu elements. Remarkably, the average length of TSS-to-first Alu intervals greatly varies inbetween tissues, being longer in stem- and shorter in immune-cells. Shortest TSS-to-Alu intervals were observed at promoters active in T cells, particularly at immune genes, correlating with serendipitous RNA polymerase II transcription and accumulation of H3K4me1 signal at the first-Alu. At several T-cell first-Alus, the DNA methylation was further found to evolved with age, regressing from young to middle-aged, then recovering later in life. Thus, the first-Alu upstream of TSSs functions as a dynamic boundary for regulatory elements, initiating the upstream DNA-methylation landscape, while also participating in the recording of immune gene transcriptional events.Competing Interest StatementThe authors have declared no competing interest.