Changing POU dimerization preferences converts Oct6 into a pluripotency inducer

� 2016 The Authors. Published under the terms of the CC BY 4.0 license The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4. Using structural and biochemical analyses, we identified a single amino acid directing binding to the respective DNA elements. A change in this amino acid decreases the ability of Oct4 to generate iPSCs, while the reverse mutation in Oct6 does not augment its reprogramming activity. Yet, with two additional amino acid exchanges, Oct6 acquires the ability to generate iPSCs and maintain pluripotency. Together, we demonstrate that cell type-specific POU factor function is determined by select residues that affect DNA-dependent dimerization.Link_to_subscribed_fulltex

Pulmonary imaging manifestations and related research progress of lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare multisystem neoplastic disease and is primarily affected women of childbearing age and premenopausal women. LAM lesions involve the lungs [known as pulmonary Lymphangioleiomyomatosis (PLAM)], kidneys [such as angiomyolipoma (AML)], and the lymphatic system (including lymphangioleiomyomas and chylous effusions). As the disease progresses, LAM disrupts lung tissue, alters lung structure, and leads to the development of lymphangioleiomyomas in the chest and abdominal lymphatic ducts. Early symptoms in LAM patients are mild, and clinical presentations lack specificity, making misdiagnosis common. Death can occur due to pulmonary function deterioration and recurrent pneumothorax. Currently, lung transplantation is considered the only effective treatment, although recurrence rates are relatively high. High-resolution computer tomography (HRCT) of the chest is a key diagnostic tool for LAM,which aid not only in the diagnosis but also in assessing the severity and prognosis of the condition. With the rapid development of medical imaging technology, particularly the use of photon counting detector CT (PCD-CT), which offers high resolution and noise reduction capabilities, significant improvements in image quality can be achieved. Compared to traditional CT scans, PCD-CT reduces radiation exposure by 35.7%, making it highly suitable for diagnosing and long-term monitoring of LAM

How to extract traditional cultural design elements from a set of images of cultural relics based on F-AHP and entropy

The creative cultural product design, relating to both typical regional cultures and traditional cultural elements, is a hot issue in recent years. However, there is still a lack of systematic and efficient designing methods to guide designing practices. In order to fill this research gap, this paper proposes a new design method based on F-AHP (Fuzzy-Analytic Hierarchy Process) and entropy computation to extract traditional cultural shape design elements from a set of images of cultural relics. Firstly, we collect a set of culture object related to descriptive and adjective words that can express users’ emotional perception and narrow down them into a shortlist via a fitness evaluation process. Secondly, we analyze and extract common shape elements with image processing tools and user choices. Thirdly, we create a full mapping between the shortlisted culture descriptive words and the identified common shape elements and determine the weighting of each shape element against each evaluation indicator through F-AHP. Fourthly, we construct decision-making matrix and extract key shape elements with high information entropy. Finally, we start designing products with extracted cultural elements. A case study of Han Dynasty potter figurines was conducted to verify the feasibility of the proposed approach

Quantitative characterization of histone post-translational modifications using a stable isotope dimethyl-labeling strategy

Histone post-translational modifications (PTMs) have been considered to be a major group of important epigenetic marks and play critical roles in the regulation of chromatin-templated biological processes. To date, novel strategies for the quantification of histone PTMs are still highly desirable. Herein, we present an efficient approach to quantitatively characterize histone PTMs using stable isotope dimethyl labeling coupled with mass spectrometry. At first, all of the 3-aminogroups of free lysines are derivatized by heavy formaldehyde to enable an easy distinction of free lysines from those of naturally occurring lysine-dimethylation upon MS analysis. After tryptic digestion, a second derivatization was applied with heavy- and light-stable isotope dimethyl labeling to label the N-termini of tryptic peptides from different sample sources. The mixture was further identified and quantified by HPLC-MS/MS. This method enables the comparison of histone PTMs from multiple sample sources and the quantification of different PTMs at certain amino-acid residues of histones in one single experiment. Thus, it is highly attractive for the identification of epigenetic histone marks

HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription

Abstract Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription