LOTUS domain is a novel class of G-rich and G-quadruplex RNA binding domain.

LOTUS domains are helix-turn-helix protein folds identified in essential germline proteins and are conserved in prokaryotes and eukaryotes. Despite originally predicted as an RNA binding domain, its molecular binding activity towards RNA and protein is controversial. In particular, the most conserved binding property for the LOTUS domain family remains unknown. Here, we uncovered an unexpected specific interaction of LOTUS domains with G-rich RNA sequences. Intriguingly, LOTUS domains exhibit high affinity to RNA G-quadruplex tertiary structures implicated in diverse cellular processes including piRNA biogenesis. This novel LOTUS domain-RNA interaction is conserved in bacteria, plants and animals, comprising the most ancient binding feature of the LOTUS domain family. By contrast, LOTUS domains do not preferentially interact with DNA G-quadruplexes. We further show that a subset of LOTUS domains display both RNA and protein binding activities. These findings identify the LOTUS domain as a specialized RNA binding domain across phyla and underscore the molecular mechanism underlying the function of LOTUS domain-containing proteins in RNA metabolism and regulation.

Mapping the Effects of Genetic Variation on Chromatin State and Gene Expression Reveals Loci That Control Ground State Pluripotency.

Mouse embryonic stem cells (mESCs) cultured in the presence of LIF occupy a ground state with highly active pluripotency-associated transcriptional and epigenetic circuitry. However, ground state pluripotency in some inbred strain backgrounds is unstable in the absence of ERK1/2 and GSK3 inhibition. Using an unbiased genetic approach, we dissect the basis of this divergent response to extracellular cues by profiling gene expression and chromatin accessibility in 170 genetically heterogeneous mESCs. We map thousands of loci affecting chromatin accessibility and/or transcript abundance, including 10 QTL hotspots where genetic variation at a single locus coordinates the regulation of genes throughout the genome. For one hotspot, we identify a single enhancer variant ∼10 kb upstream of Lifr associated with chromatin accessibility and mediating a cascade of molecular events affecting pluripotency. We validate causation through reciprocal allele swaps, demonstrating the functional consequences of noncoding variation in gene regulatory networks that stabilize pluripotent states in vitro.

Osteoarthritis of the temporomandibular joint and increase of the horizontal condylar angle: a longitudinal study.

OBJECTIVE: Our previous study of patients with unilateral temporomandibular joint (TMJ) osteoarthritis (OA) showed that the affected joints had greater horizontal condylar angle (HCA) compared with the contralateral unaffected joints. However, it was unclear whether the HCA changes preceded or were the result of OA changes. The aim of this longitudinal study was to investigate the relationship between HCA and OA progression. STUDY DESIGN: In total, 127 patients (with or without TMJ disorders) completed baseline and follow-up examinations (average time to follow-up 7.9 years). Generalized estimating equation models were used to account for correlation of observations within the same patients. RESULTS: (1) HCA was greater in OA-affected joints than in unaffected joints (P = .04). (2) Increased HCA at follow-up was associated with change in joint status from no OA to OA. (P = .001). (3) Baseline HCA value alone did not predict future OA diagnosis. (4) All OA changes in fossa/articular eminence morphology, and some combinations of condylar changes, were associated with a greater HCA. (5) OA diagnosis was associated with pain during maximum opening (P = .005) and pain history (P = .002). (6) Aging alone was not correlated with increased HCA. CONCLUSIONS: Clinical progression of OA preceded increases in HCA. HCA alone did not predict OA development.

Greater mandibular horizontal condylar angle is associated with temporomandibular joint osteoarthritis.

BACKGROUND: Research using magnetic resonance imaging analysis has shown that internal temporomandibular joint derangement is associated with significantly greater horizontal condylar angle. However, the association between osteoarthritic (OA) bony changes as shown on computed tomography and horizontal condylar angle has never been evaluated. OBJECTIVE: To investigate the relationship between mandibular condylar angle and OA degenerative changes. STUDY DESIGN: This is a retrospective study using cone beam computed tomography images and reports from 60 patients with unilateral OA degenerative changes and 43 control patients with no OA-affected joints. RESULTS: Condylar angles in the joints of control patients and the unaffected joints in OA patients were not significantly different. The mean horizontal condylar angle in the unilaterally OA-affected joints (29.5° ± 10.5°) was larger than in the contralateral unaffected joints (22.5° ± 7.7°) (P < .001). In the OA-affected joints, flattening and erosion of the articular eminence was associated with a greater condylar angle (P < .05). CONCLUSIONS: Moderate to severe degenerative temporomandibular joint change is associated with greater horizontal condylar angle.