Genome-wide prediction and analysis of human chromatin boundary elements

Abstract

Boundary elements partition eukaryotic chromatin into active and repressive domains, and can also block regulatory interactions between domains. Boundary elements act via diverse mechanisms making accurate feature-based computational predictions difficult. Therefore, we developed an unbiased algorithm that predicts the locations of human boundary elements based on the genomic distributions of chromatin and transcriptional states, as opposed to any intrinsic characteristics that they may possess. Application of our algorithm to ChIP-seq data for histone modifications and RNA Pol II-binding data in human CD4+ T cells resulted in the prediction of 2542 putative chromatin boundary elements genome wide. Predicted boundary elements display two distinct features: first, position-specific open chromatin and histone acetylation that is coincident with the recruitment of sequence-specific DNA-binding factors such as CTCF, EVI1 and YYI, and second, a directional and gradual increase in histone lysine methylation across predicted boundaries coincident with a gain of expression of non-coding RNAs, including examples of boundaries encoded by tRNA and other non-coding RNA genes. Accordingly, a number of the predicted human boundaries may function via the synergistic action of sequence-specific recruitment of transcription factors leading to non-coding RNA transcriptional interference and the blocking of facultative heterochromatin propagation by transcription-associated chromatin remodeling complexes.