A comparative encyclopedia of DNA elements in the mouse genome

Abstract

SummaryAs the premier model organism in biomedical research, the laboratory mouse shares the majority of protein-coding genes with humans, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications, and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

“…Since MyoD is a master regulator of myogenesis, plays a pivotal role in enhancer assembly [16], and may cooperate with p300 to promote early myoblast differentiation (Figure 2(c)), we thus also annotated publicly available genome-wide MyoD ChIP-seq data in proliferating C2C12 myoblasts and myoblasts differentiated for 24 hours [40]. Union analysis of MyoD binding sites across the two conditions revealed twice as many MyoD peaks unique to differentiation compared to proliferation (Figure 3(a)), highlighting the requirement of MyoD to control the transcriptional program pertinent to differentiation.…”

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

“…To check if Flnc mRNA also undergoes A-to-I editing at this overlapping position (chr6:29,457,557) amplicons from wild type adult mouse tissues where Flnc is mainly expressed [11,12] were analysed by Sanger sequencing. No A-G transitions were detected in heart, skeletal muscle or bladder samples (Figure 4).…”

“…In vertebrates, filamin A, B, and C (FLNA, FLNB, FLNC) are known. By homology, FLNC is most distant and exclusively expressed in a few tissues, such as heart, skeletal muscles and bladder [11,12]. In contrast, FLNA and FLNB are highly homologous and ubiquitously expressed [13].…”

Two independent modes of chromatin organization revealed by cohesin removal

“…To find the average footprint of a chromatin-bound CTCF, we detected all occurrences of the M1 CTCF motif 53 in the mm9 genome (filtered by p-value > 0.0001), intersected with CTCF binding peaks in ENCODE adult mouse liver dataset 54 . This procedure yielded 27840 peaks.…”