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However for many types of histone modifications, the distribution of reads obeys a continuous property, as the epigenetic status of nearby nucleosomes tend to be similar, usually resulting in quite broad peaks. For most TFs, sequencing reads enriched regions are generally discrete, and typically they form sharp peaks along the genome. Although the procedure to generate histone modification ChIP-Seq data is quite similar to that for cistrome, the distributions of sequencing reads for both cases are usually different.
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As different histone modifications have distinct effects on chromatin environments by altering the binding to DNA or providing recognition sites for chromatin effector modules, genome-wide ChIP-Seq approaches can dramatically increase the understanding on the relationships between specific histone modifications and gene regulation outcomes. Secondly, MACS estimates a dynamic background reads distribution to effectively capture local biases in the genome, allowing for more robust identifications.īesides cistrome studies, ChIP-Seq technology is also widely used to generate epigenome profiles, especially histone modification status ( Barski, et al., 2007 Mikkelsen, et al., 2007). Firstly, MACS empirically models the shift size of ChIP-Seq reads, and uses it to improve the spatial resolution of inferred TF binding sites. MACS was originally designed to give robust and high resolution peak identification for ChIP-Seq data with two main features ( Zhang, et al., 2008). The enriched DNA fragments are then sequenced using massively parallel DNA sequencing technology, with outputs called sequencing reads or tags.
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Briefly, in the ChIP step, DNA sequences are fragmentized into hundreds of base pairs, and fragments with certain TF binding are enriched through immunoprecipitation. To uncover the regulation mechanisms, one promising approach is to identify all cis-acting targets, or called binding sites, for a given TF in the genome scale, which is defined as the TF’s cistrome ( Carroll, et al., 2006 Lupien, et al., 2008), and the popular technology to study cistrome is Chromatin Immunoprecipitation coupled with sequencing (ChIP-Seq) ( Johnson, et al., 2007). One type of special proteins, called transcription factors (TFs), performs important functions by regulating the transcription of genes via physically interaction with certain DNA sequence patterns, or called motifs.