Chromatin Modifications and Their Function

High-resolution profiling of histone methylations in the human genome.

http://www.people.vcu.edu/~mreimers/SysBio/Li%20-%20Role%20of%20chromatin%20in%20transcription.pdf

The Role of Chromatin during Transcription

Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome.

https://zlab.umassmed.edu/zlab/publications/HeintzmanChromatinSignatureNatGenetics.pdf

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.

An altered pattern of epigenetic modifications is central to many common human diseases, including cancer. Many studies have explored the mosaic patterns of DNA methylation and histone modification in cancer cells on a gene-by-gene basis; among their results has been the seminal finding of transcriptional silencing of tumour-suppressor genes by CpG-island-promoter hypermethylation. However, recent technological advances are now allowing cancer epigenetics to be studied genome-wide — an approach that has already begun to provide both biological insight and new avenues for translational research. It is time to 'upgrade' cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using epigenomics approaches.

http://genetique.snv.jussieu.fr/OLD%20SITE/documents%202010/NB217/Articles_2009/Twin%20stduies_SB/Esteller_review_2007.pdf

Cancer epigenomics: DNA methylomes and histone-modification maps

DNA-binding transcriptional regulators interpret the genome's regulatory code by binding to specific sequences to induce or repress gene expression. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation, but this information alone does not reveal if or when transcriptional regulators occupy these binding sites. We have constructed an initial map of yeast's transcriptional regulatory code by identifying the sequence elements that are bound by regulators under various conditions and that are conserved among Saccharomyces species. The organization of regulatory elements in promoters and the environment-dependent use of these elements by regulators are discussed. We find that environment-specific use of regulatory elements predicts mechanistic models for the function of a large population of yeast's transcriptional regulators.

/pdf/transcriptional-regulatory-code-of-a-eukaryotic-genome-2df92bvrme.pdf

P. Alex Rolfe

Papers

Transcriptional regulatory code of a eukaryotic genome

Genome-wide map of nucleosome acetylation and methylation in yeast.