https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/159777/1/j.cell.2006.07.024.pdf

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

/pdf/identification-and-analysis-of-functional-elements-in-1-of-2o640l8ikl.pdf

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.

Long non-coding RNAs: insights into functions

Evolution and functions of long noncoding RNAs

https://bioinformatics.cs.vt.edu/%7Eeasychair/CawleyEtAl_Cell_2004.pdf

Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs.

Alternative splicing is a major source of variety in mammalian mRNAs, yet many questions remain on its downstream effects on protein function. To this end, we assessed the impact of gene structure and splice variation on signal peptide and transmembrane regions in proteins. Transmembrane proteins perform several key functions in cell signaling and transport, with their function tied closely to their transmembrane architecture. Signal peptides and transmembrane regions both provide key information on protein localization. Thus, any modification to such regions will likely alter protein destination and function. We applied TMHMM and SignalP to a nonredundant set of proteins, and assessed the effects of gene structure and alternative splicing on predicted transmembrane and signal peptide regions. These regions were altered by alternative splicing in roughly half of the cases studied. Transmembrane regions are divided by introns slightly less often than expected given gene structure and transmembrane region size. However, the transmembrane regions in single-pass transmembranes are divided substantially less often than expected. This suggests that intron placement might be subject to some evolutionary pressure to preserve function in these signaling proteins. The data described in this paper is available online at http://www.affymetrix.com/community/publications/affymetrix/tmsplice/.

/pdf/the-effects-of-alternative-splicing-on-transmembrane-1c6kdkscp3.pdf

The effects of alternative splicing on transmembrane proteins in the mouse genome.

Many researchers have focused their attention on alternative splice forms of genes as a means to explain the apparent complexity of human and other higher eukaryotic organisms. The exon-intron structure implied by aligning ESTs and mRNAs to genomic sequence provides a useful basis for comparing different splice forms. There are software tools that enumerate all possible exon-intron combinations implied by these alignments, but this approach has potential drawbacks including a combinatorial explosion in the number of splice forms and the generation of many unsupported splice forms. altMerge retains information about exon combinations present in the input alignments. It uses this information to combine compatible subsets of the alignments into a single representative form. Substructures of these representative forms are then exchanged to enumerate only those alternative splice forms that are consistent with the input alignments.

A Method of Consolidating and Combining EST and mRNA Alignments to a Genome to Enumerate Supported Splice Variants

In one embodiment of the invention, computerized methods are provided for analyzing transcript sequence clusters by aligning the transcripts with genomic sequences to determine whether a cluster needs to be sub-clustered and whether clusters should be merged. In addition, in some embodiments, transcript sequences are trimmed according to their alignment with their corresponding genomic sequences. The modified clusters and trimmed sequences may be used for nucleic acid probe array design.

Method and computer software product for genomic alignment and assessment of the transcriptome

In one embodiment of the invention, methods are provided for selecting probes upstream from alternative polyadenylation sites of a target sequence cluster.

Raymond Wheeler

Papers

Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs.

The effects of alternative splicing on transmembrane proteins in the mouse genome.

A Method of Consolidating and Combining EST and mRNA Alignments to a Genome to Enumerate Supported Splice Variants

Method and computer software product for genomic alignment and assessment of the transcriptome

Method and computer software product for defining multiple probe selection regions