ENCODE, the Encyclopedia Of DNA Elements is a public research consortium launched by NHGRI in september 2003. The project is to identify all the functional elements in the human genome sequence.
The goal is to map a variety of sequence elements including genes, promoters, enhancers, repressor or silencer sequences, exons, replication origin and termination sites, transcription factor binding sites, methylation sites, DNase I hypersensitive sites, chromatin modifications, conserved sequences, and RNA transcripts, to name a few.
Results of the analysis of targeted 1% human genome are provided for Free access.
Highlights of the finding are (source -.www.nature.com)
- The human genome is pervasively transcribed, such that the majority of its bases are associated with at least one primary transcript and many transcripts link distal regions to established protein-coding loci.
- Many novel non-protein-coding transcripts have been identified, with many of these overlapping protein-coding loci and others located in regions of the genome previously thought to be transcriptionally silent.
- Numerous previously unrecognized transcription start sites have been identified, many of which show chromatin structure and sequence-specific protein-binding properties similar to well-understood promoters.
- Regulatory sequences that surround transcription start sites are symmetrically distributed, with no bias towards upstream regions.
- Chromatin accessibility and histone modification patterns are highly predictive of both the presence and activity of transcription start sites.
- Distal DNaseI hypersensitive sites have characteristic histone modification patterns that reliably distinguish them from promoters; some of these distal sites show marks consistent with insulator function.
- DNA replication timing is correlated with chromatin structure.
- A total of 5% of the bases in the genome can be confidently identified as being under evolutionary constraint in mammals; for approximately 60% of these constrained bases, there is evidence of function on the basis of the results of the experimental assays performed to date.
- Although there is general overlap between genomic regions identified as functional by experimental assays and those under evolutionary constraint, not all bases within these experimentally defined regions show evidence of constraint.
- Different functional elements vary greatly in their sequence variability across the human population and in their likelihood of residing within a structurally variable region of the genome.
- Surprisingly, many functional elements are seemingly unconstrained across mammalian evolution. This suggests the possibility of a large pool of neutral elements that are biochemically active but provide no specific benefit to the organism. This pool may serve as a 'warehouse' for natural selection, potentially acting as the source of lineage-specific elements and functionally conserved but non-orthologous elements between species.
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