6/10/2023 0 Comments Imagezilla set2![]() Our structure shows that Set2 makes extensive interactions with H3 αN, H3 tail, H2A C-terminal tail, and stabilizes DNA in an unwrapped conformation 42. In this study, we present 3.8 Å cryo-EM structure of Set2 bound to the mimic of H2B ubiquitinated nucleosome core particle (NCP) 41. These findings show that overexpression or mutation of Set2 enzymes or H3K36 promote cancer progression.Īlthough Set2 involvement in essential cellular processes is well described, mechanisms of Set2 mediated H3K36 methylation are poorly understood. Set2 family enzymes are overexpressed in multiple myeloma, neuroblastoma, bladder and breast cancers, and correlate with poor prognosis 3, 37, 38, 39, 40. H3.3K36M mutation traps SETD2 methyltransferase on the substrate which results in genome-wide loss of H3K36 methylation and tumor formation 33, 35. Recently, mutation of H3.3K36 to methionine has been found in chondroblastomas, head and neck squamous cell carcinoma, and colorectal cancer 31, 32, 33, 34, 35, 36. In animals, Set2 family enzymes are essential for maintenance of cell identity 26, 27 and are mutated in many patients with clear cell renal cell carcinoma, acute leukemias, bladder cancer, and glioblastoma 28, 29, 30. Recent data show that Set2 and H3K36me are also involved in DNA damage repair 18, 19, 20, regulation of pre-mRNA splicing 21, 22, chromatin condensation 23, and histone exchange 24, 25. Although deposited by the transcription machinery, H3K36me seems to be a silencing mark that prevents initiation of cryptic transcription within gene bodies 2, 15, 16, 17. H3K36me recruits Rpd3S histone deacetylase complex to restore a repressed chromatin state behind the elongating polymerase 13, 14. Both, H3K36me and H2B K120 ubiquitination are enriched over gene bodies 12. In addition to Set2, RNA Polymerase 2 elongation complex recruits Bre1/Rad6 that ubiquitinate H2B K120 10, 11, indicating possible interplay between these two histone modifications. Set2 is recruited by phosphorylated C-terminal domain of RNA Polymerase 2 during transcription and catalyzes H3K36 methylation over gene bodies 4, 5, 6, 7, 8, 9. One of the essential histone modifications, histone H3 lysine 36 methylation (H3K36me) is deposited by the Set2 methyltransferase onto the H3 tail and is conserved from yeast to humans 2, 3. Histone modifications are a key player in maintaining genome stability, chromosome segregation, and genome expression 1. Notably, our structure uncovers interfaces that can be targeted by small molecules for development of future cancer therapies. Moreover, we show that ubiquitin contributes to Set2 positioning on the nucleosome and stimulates the methyltransferase activity. Our structure shows that Set2 makes extensive interactions with the H3 αN, the H3 tail, the H2A C-terminal tail and stabilizes DNA in the unwrapped conformation, which positions Set2 to specifically methylate H3K36. In this study, we present 3.8 Å cryo-EM structure of Set2 bound to the mimic of H2B ubiquitinated nucleosome. Set2 enzymes show spurious activity on histones and histone tails, and it is unknown how they obtain specificity to methylate H3K36 on the nucleosome. Recent findings show that over-expression or mutation of Set2 enzymes promotes cancer progression, however, mechanisms of H3K36me are poorly understood. The recommended size for a header display image is 1200 pixels wide (height to maintain aspect ratio).Histone H3 lysine 36 methylation (H3K36me) is a conserved histone modification deposited by the Set2 methyltransferases. This image size would be absolutely fine for the photo gallery, but will look slightly poor and perhaps pixelated uploaded as a header image display. So in this particular instance the photo is 425 pixels: ![]() Then to see what pixel size it is click into 'Details' and scroll down until you see 'Image' and then 'Dimensions'. This allows you to see the size of the photo file. If you're unsure of the image quality, a good check is to right click on the image where it is saved on your computer, then click into 'Properties' and the following pop-up will appear on your screen: You do not crop in too much to your image which will distort the pixelation.You are uploading the original photo to your website, not an image copied and saved from another website or social media channel.Your photo has been taken with a good camera and is of a high resolution.To alleviate this problem make sure of the following: the smaller you make the crop the more blurry the image, but higher resolution images can cope better with this. If you've uploaded images to your website yet when viewing them in Preview, or in Live mode, they appear blurry it is likely to be due to a combination of the original picture quality and the size of the crop you have set i.e.
0 Comments
Leave a Reply. |