The study by Wang et al. (2009) investigates the regulation of alternative isoforms in human tissues and cell lines using deep sequencing of cDNA fragments. The analysis reveals that 92-94% of human genes undergo alternative splicing (AS), with ~86% showing minor isoform frequencies of 15% or more. The majority of AS and alternative cleavage and polyadenylation (APA) events vary between tissues, while individual variation is less common. Extreme or 'switch-like' regulation of splicing between tissues is associated with increased sequence conservation in regulatory regions and the generation of full-length open reading frames. Patterns of AS and APA are strongly correlated across tissues, suggesting coordinated regulation. The study also identifies novel exons and splice junctions and assesses the extent of tissue-specific regulation of alternative transcripts, finding that over 22,000 tissue-specific events were identified. Individual-specific variation in alternative isoform expression was also observed, but it was less frequent than tissue-specific variation. The authors further explore the properties of switch-like exons, which exhibit dramatic differences in inclusion levels between tissues, and infer a tissue-specific regulatory activity map using the Fox-1/-2 proteins. They also examine the coordination between splicing and polyadenylation, finding that these processes may be regulated by the same factors. Overall, the study highlights the pervasive and tissue-specific nature of AS and APA in human transcriptomes.The study by Wang et al. (2009) investigates the regulation of alternative isoforms in human tissues and cell lines using deep sequencing of cDNA fragments. The analysis reveals that 92-94% of human genes undergo alternative splicing (AS), with ~86% showing minor isoform frequencies of 15% or more. The majority of AS and alternative cleavage and polyadenylation (APA) events vary between tissues, while individual variation is less common. Extreme or 'switch-like' regulation of splicing between tissues is associated with increased sequence conservation in regulatory regions and the generation of full-length open reading frames. Patterns of AS and APA are strongly correlated across tissues, suggesting coordinated regulation. The study also identifies novel exons and splice junctions and assesses the extent of tissue-specific regulation of alternative transcripts, finding that over 22,000 tissue-specific events were identified. Individual-specific variation in alternative isoform expression was also observed, but it was less frequent than tissue-specific variation. The authors further explore the properties of switch-like exons, which exhibit dramatic differences in inclusion levels between tissues, and infer a tissue-specific regulatory activity map using the Fox-1/-2 proteins. They also examine the coordination between splicing and polyadenylation, finding that these processes may be regulated by the same factors. Overall, the study highlights the pervasive and tissue-specific nature of AS and APA in human transcriptomes.