The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.

Self-Assembled Heterojunction Carbon Nanotubes Synergizing with Photoimmobilized IGF-1 Inhibit Cellular Senescence.

Synthesis of artificial and functional structures for bone tissue engineering has been well recognized but the associated cell senescence issue remains much less concerned so far. In this work, surface-modified polycaprolactone-polylactic acid scaffolds using self-assembled heterojunction carbon nanotubes (sh-CNTs) combined with insulin-like growth factor-1 are synthesized and a series of structural and biological characterizations are carried out, with particular attention to cell senescence mechanism. It is revealed that the modified scaffolds can up-regulate the expressions of alkaline phosphates and bone morphogenetic proteins while down-regulate the expressions of senescence-related proteins in mesenchymal stem cells, demonstrating the highly preferred anti-senescence functionality of the sh-CNTs modified scaffolds in bone tissue engineering. Furthermore, it is also found that with sh-CNTs, scaffolds can accelerate bone healing with extremely low toxicity in vivo.

Splenic littoral cell hemangioendothelioma: report of a case with hepatic metastases and review of the literature.

Littoral cell tumors are unique to the spleen and are different from all other primary splenic tumors. These tumors may be divided into three types: "littoral cell angioma," "littoral cell hemangioendothelioma," and "littoral cell angiosarcoma." We present a patient with splenic littoral cell hemangioendothlioma accompanied by hepatic metastases.

Imprinting and Promoter Usage of Insulin-Like Growth Factor II in Twin Discordant Placenta.

Case reports from infant twins suggest that abnormal genomic imprinting may be one of the important causes of twin discordance, but it is unknown whether abnormal genomic imprinting occurs in the placenta. Therefore, we sought to determine the relationship between the imprinting of insulin-like growth factor II (IGF-II) in placenta and twin discordance. We analyzed the imprinting and promoter usage of IGF-II in placenta of normal twins (T0 group), weight discordance (T1 group), and phenotype discordance (T2 group). We found the incidence of loss of imprinting (LOI) for IGF-II was higher in the T2 group than that in the T0 and T1 groups, while there was no difference between T0 and T1 groups. The transcripts of promoter 3 were lower in the T2 group than in the T0 and T1 groups, and lower in the twin placenta with LOI than in those with normal imprinting. Our findings indicate that the promoter 3 specific LOI of the IGF-II gene may be closely related with phenotype discordance, not weight discordance.

Analysis of catharanthine content and agronomic traits in Catharanthus roseus / 中国中药杂志

Catharanthine content and agronomic traits in major Catharanthus roseus varieties were analyzed. It was found that there existed great difference in catharanthine content and agronomic traits among the varieties. Catharanthine content was the highest in variety Pacifica Polka Dot (PPD), reaching 3.79 mg g(-1) dry leaf weight, and the lowest in variety Cooler Pink (CP) with only 0.9 mg g(-1) dry leaf weight. Correlation existed in certain extent between catharanthine content and agronomic traits in C. roseus. Path analysis showed that among all the agronomic traits analyzed, internodal distance positively affected catharanthine content at significant level (P<0.05), with the path coefficient being 1.473. This study provides useful information for high-catharanthine content C. roseus introduction and breeding.

[Characteristics of IGF-II gene imprinting in twin placentas].

OBJECTIVE: To compare insulin-like growth factor II (IGF-II) gene imprinting in twin placentas with singleton ones and to determine whether imprinting was influenced by assisted reproductive technology, zygosity and fetal sex. METHODS: One hundred and sixty cases of twin placentas and 42 cases of singleton ones were recruited. Allele-specific IGF-II expression was determined by reverse transcription-PCR combined with analysis of an Apa I-sensitive restriction fragment length polymorphism. RESULTS: Although the incidence of IGF-II imprinting loss was higher in normal twin placentas than in singleton ones (20.6% vs 8.7%), there was no statistical significance. There were no significant differences between twins conceived by assisted reproductive technology and those conceived spontaneously (17.9% vs 24.4%), and between dizygotic and monozygotic twins (22.4% vs 16.7%). The incidence of IGF-II imprinting loss in placenta of female twins was statistically higher than that of male ones (26.4% vs 9.8%). CONCLUSION: The risk of IGF-II gene imprinting loss is higher in female twins and has no relationship with assisted reproductive technology and zygosity.

Characteristics of IGF-II gene imprinting in twin placentas / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To compare insulin-like growth factor II (IGF-II) gene imprinting in twin placentas with singleton ones and to determine whether imprinting was influenced by assisted reproductive technology, zygosity and fetal sex.</p><p><b>METHODS</b>One hundred and sixty cases of twin placentas and 42 cases of singleton ones were recruited. Allele-specific IGF-II expression was determined by reverse transcription-PCR combined with analysis of an Apa I-sensitive restriction fragment length polymorphism.</p><p><b>RESULTS</b>Although the incidence of IGF-II imprinting loss was higher in normal twin placentas than in singleton ones (20.6% vs 8.7%), there was no statistical significance. There were no significant differences between twins conceived by assisted reproductive technology and those conceived spontaneously (17.9% vs 24.4%), and between dizygotic and monozygotic twins (22.4% vs 16.7%). The incidence of IGF-II imprinting loss in placenta of female twins was statistically higher than that of male ones (26.4% vs 9.8%).</p><p><b>CONCLUSION</b>The risk of IGF-II gene imprinting loss is higher in female twins and has no relationship with assisted reproductive technology and zygosity.</p>

[Perinatal outcome of discordant twin pregnancies].

OBJECTIVE: To discuss peripartum obstetrics events and perinatal outcomes of discordant twin pregnancies. METHODS: Discordant growth was defined as the intrapair difference in birth weight more than 20%. Ninety-six discordant twin pregnancies (observed group) and 349 concordant ones (control group) were compared in pregnant complications and perinatal outcomes. RESULTS: No difference of maternal age, chorionicity, methods of conception and fetal gender were found between two groups. Observed group had a higher incidence of late abortion (13.5% vs 4.3%, P < 0.05), polyhydramnios (22.9% vs 10.0%, P < 0.01), twin-twin transfusion syndrome (9.4% vs 1.4%, P < 0.01), placental abruption (5.2% vs 1.1%, P < 0.05), perinatal death (22.9% vs 4.4%, P < 0.01) and of fetal malformation (5.2% vs 1.3%, P < 0.01) than control group. In observed group, perinatal death was higher in smaller twin than in larger one (30.2% vs 15.6%, P < 0.05). The incidences of perinatal death were 4.4%, 11.0% and 41.9% and fetal malformation were 1.3%, 5.1% and 5.4% when the discordance was < or = 20%, 20%-30%, and > or = 30%, respectively (P < 0.05). CONCLUSIONS: Discordance places twins at increased risk for late abortion, premature delivery, polyhydramnios, twin-twin transfusion syndrome, placental abruption, perinatal death and fetal malformation. The smaller twin and great discordance are risk factors for poor outcomes. Chorionicity, methods of conception and fetal gender are not responsible for discordant growth.