Origin of phenotypes: Genes and transcripts.

TR Gingeras — 2007-06-21T09:01:25-00:00

Genome Res, Vol. 17, No. 6. (June 2007), pp. 682-690.

While the concept of a gene has been helpful in defining the relationship of a portion of a genome to a phenotype, this traditional term may not be as useful as it once was. Currently, "gene" has come to refer principally to a genomic region producing a polyadenylated mRNA that encodes a protein. However, the recent emergence of a large collection of unannotated transcripts with apparently little protein coding capacity, collectively called transcripts of unknown function (TUFs), has begun to blur the physical boundaries and genomic organization of genic regions with noncoding transcripts often overlapping protein-coding genes on the same (sense) and opposite strand (antisense). Moreover, they are often located in intergenic regions, making the genic portions of the human genome an interleaved network of both annotated polyadenylated and nonpolyadenylated transcripts, including splice variants with novel 5' ends extending hundreds of kilobases. This complex transcriptional organization and other recently observed features of genomes argue for the reconsideration of the term "gene" and suggests that transcripts may be used to define the operational unit of a genome.

Regulation of transcript elongation through cooperative and ordered recruitment of cofactors

Manish Sharma — 2007-05-31T12:25:27-00:00

J. Biol. Chem. (29 May 2007), M701420200.

We studied the regulation of murine CD80, a gene whose basal transcriptional status was characterized by the presence of a stalled RNA polymerase II complex on the promoter-proximal region. Stimulus-induced activation of productive elongation involved a complex interplay of regulated events that included a synergy between ordered co-factor recruitment. This cascade of recruitments was initiated through the engagement of transcription factor NF-[kappa]B, leading to the temporal association of histone acetyltransferases and the consequent selective acetylation of a transcription start site-downstream nucleosome. This in turn culminated into the nucleosomal association of Brd4-associated P-TEFb, a protein complex containing kinase specific for serine 2 of Rbp 1, the largest subunit of carboxyl terminal domain (CTD) of RNA polymerase II. The consequent phosphorylation of serine 2 residues in CTD by CDK9 in P-TEFb complex then facilitated escape of polymerase II into the productive elongation phase. Thus, the cooperative mechanisms that integrate between independent pathways characterize regulation of the elongation step of transcription; thereby providing another level at which specificity of gene regulation can be achieved. 10.1074/jbc.M701420200

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Origin of phenotypes: Genes and transcripts.

Regulation of transcript elongation through cooperative and ordered recruitment of cofactors