How stage-specific enhancer dynamics modulate gene expression patterns essential for organ development, homesostasis, and disease is not well understood. Here, we addressed this question by mapping chromatin occupancy of GATA4—a master cardiac transcription factor—in heart development and disease. We find that GATA4 binds and participaes in establishing active chromatin regions by stimulating H3K27ac deposition, which facilitates GATA4-driven gene expression. GATA4 chromatin occupancy changes markedly between fetal and adult heart, with a limitted binding sites overlap. Cardiac stress restored GATA4 occupancy to a subset of fetal sites, but many stress-associated GATA4 binding sites localized to loci not occupied by GATA4 during normal heart development. Collectively, our data show that dynamic, context-specific transcription factors occupancy underlies stage-specific events in development, homeostasis, and disease.

Escherichia coli (E. coli) is one of the most frequent and lethal causes of bloodstream infections (BSIs). We carried out a retrospective multicenter study on antimicrobial resistance and phylogenetic background of clinical E. coli isolates recovered from bloodstream in three hospitals in Shanghai. E. coli isolates causing BSIs were consecutively collected between Sept 2013 and Sept 2014. Ninety isolates randomly selected (30 from each hospital) were enrolled in the study. Antimicrobial susceptibility testing was performed by disk diffusion. PCR was used to detect antimicrobial resistance genes coding for β-lactamases (TEM, CTX-M, OXA, etc.), carbapenemases (IMP, VIM, KPC, NDM-1 and OXA-48), and phylogenetic groups. eBURST was applied for analysis of multi-locus sequence typing (MLST). The resistance rates for penicillins, second-generation cephalosporins, fluoroquinolone and tetracyclines were high (>60%). Sixty-one of the 90 (67.8%) strains enrolled produced ESBLs and no carbapenemases were found. Molecular analysis showed that CTX-M-15 (25/61), CTX-M-14 (18/61) and CTX-M-55 (9/61) were the most common ESBLs. Phylogenetic group B2 predominated (43.3%) and exhibited the highest rates of ESBLs production. ST131 (20/90) was the most common sequence type and almost assigned to phylogenetic group B2 (19/20). The following sequence types were ST405 (8/90) and ST69 (5/90). Among 61 ESBL-producers isolates, B2 (26, 42.6%) and ST131 (18, 29.5%) were also the most common phylogenetic group and sequence type. Genetic diversity showed no evidence suggesting a spread of these antimicrobial resistant isolates in the three hospitals. In order to provide more comprehensive and reliable epidemiological information for preventing further dissemination, well-designed and continuous surveillance with more hospitals participating was important.

Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing pneumonia among children. To estimate the prevalence and molecular properties of S. aureus in children pneumonia in Shanghai, China, 107 hospitalized children with S. aureus pneumonia from two children's hospitals from January 2014 through June 2015 were studied. S. aureus isolates from the respiratory specimens were characterized by antimicrobial susceptibility, agr typing, toxin genes, multilocus sequence typing (MLST), spa, and SCCmec typing. Fifty-eight (54.2%, 58/107) were MSSA (methicillin-susceptible Staphylococcus aureus) and 49 (45.8%, 49/107) were MRSA. No isolates were found resistant to teicoplanin, sulfamethoxazole/trimethoprim, rifampicin, quinupristin/dalfopristin, linezolid, or vancomycin. However, these isolates showed high resistant rates to erythromycin, fosfomycin-trometamol and clindamycin. The agrI (87/107, 81.3%) was the most common agr allele, followed by agrIII(10/107, 9.3%), agrII(9/107, 8.4%), and agrIV(1/107, 0.9%). Six pvl-positive isolates (3 MRSA and 3 MSSA) and 7 isolates of livestock associated clone ST398 (4 MRSA, 3 MSSA) were identified. CC59 was found in 35 isolates (33 MRSA and 2 MSSA), constituting majority of MRSA (33/49, 67.35%). The dominant CC were CC59 (32.7%), CC188 (13.1%), CC7 (12.1%) and CC398 (9.3%) while t172 (16.8%), t189 (12.1%), t437 (9.3%), and t091 (9.3%) were the most common spa types. In conclusion, more particular concern should appeal to ST59-SCCmecIV-t172/t437 as it is the most common epidemic clone causing pneumonia among children in Shanghai.