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Epigenetic control of genome function is a key regulatory mechanism in diverse processes such as lineage commitment and environmental sensing, and in disease etiologies ranging from neuropsychiatric disorders to cancer. Chemical modifications to DNA and histone proteins constitute an important effector of epigenetic control. Recently, therapeutics that modulates levels of these modifications has been brought to the clinic and further development of drugs in this class is ongoing.
Chromatin is composed of DNA, histones and non-histone proteins. In forming chromatin, DNA is tightly wrapped around histones. Histone proteins are subject to a wide range of covalent posttranslational modifications (PTMs), such as phosphorylation, acetylation, and methylation. These chemical moieties alter the architecture of chromatin or serve as docking sites for ‘‘reader’’ proteins that dictate higher-order chromatin compaction or recruit protein complexes with DNA-related biological functions. Nucleosomes constituted with histone variants change the structure and stability of chromatin and, through unique protein motifs or variant-specific PTMs, alter interactions with chromatin binding proteins. Collectively, chromatin modifications (chromatin marks), including histone PTMs and histone variants, along with the underlying DNA, regulate epigenetic phenotypes. Despite the crucial roles of chromatin marks in diverse physiological functions and human diseases, studying chromatin biology in human immune cells has been challenging.
Figure 1. The formation of Chromatin.
As a biotechnology company specializing in epigenomics profiling services, Creative Biogene can provide a series of chromatin analysis services which utilize a range of techniques to ascertain the 3D structure and chemical modifications of chromatin. These techniques examine the locations of histone modifications or transcription factors.
Chromatin Immunoprecipitation (ChIP) Techniques
Chromatin immunoprecipitation (ChIP) offers an advantageous method for studying protein-DNA interactions and can be used to determine whether a specific protein binds to a particular sequence of a gene, such as the target sequence of a transcription factor or to compare the levels of histone methylation associated with a specific gene promoter region between normal and diseased tissues. Our ChIP-seq (chromatin immunoprecipitation sequencing) or ChIP-qPCR (chromatin immunoprecipitation quantitative PCR) services allow you to make the most of your chromatin studies with minimal sequencing bias. The ChIP-seq/ChIP-qPCR services include:
Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) is an approach for mapping chromatin accessibility genome-wide. This method probes DNA accessibility with hyperactive Tn5 transposase, which inserts sequencing adapters into accessible regions of chromatin. Then, sequencing reads can be used to infer regions of increased accessibility, as well as to map regions of transcription factor binding and nucleosome position. Creative Biogene can provide a comprehensive range of ATAC-seq services to help you:
1) Gain insight into gene regulation and open chromatin signatures;
2) Uncover TF occupancy;
3) Determine nucleosome positions at single nucleotide resolution;
4) Benefit from comprehensive services – tagmentation, library preparation, sequencing, and analysis.
Chromosome Conformation Capture
Chromosome conformation capture (3C) is a technique that is used to detect the spatial organization of chromosomal DNA in fixed cells. DNA sequences in spatial proximity in the nucleus or engaged in physical interactions can be assessed quantitatively to provide a measure which potentially reflects their frequency of association and/or their proximity. 3C can be used to study long-range interactions between DNA sequences on the same chromosome (intrachromosomal) or between different chromosomes (interchromosomal).
Figure 2. Chromosome conformation capture (3C).
With high-level scientific expertise and specialized resources, Creative Biogene has developed a series of 3C Based Techniques services, including Circularized Chromosome Conformation Capture (4C), Carbon Copy Chromosome Conformation Capture (5C), ChIP-Loop, Hi-C and Capture-C.
Based on the most comprehensive chromatin analysis services, Creative Biogene can help you profile histone modifications and transcription factor binding genome-wide to understand the regulation of gene expression in disease or in response to a drug treatment. If you have any specific needs, please feel free to contact us. Look forward to the cooperation with you in the near future.