On 2016 Apr 14, RODERIC GUIGO commented:

The literature cite by Eduard is relevant to the topic of the relationship between histone modifications and splicing. These works, as well as others, show that there is a weak (and sometimes controversial) effect of histone modifications and exon inclusion. This weak effect could reflect a general weak effect on most exons, or a stronger effect on a smaller set of exons. The main contribution of Curado et al. (2015) is the identification of a small set of exons in which histone modifications seem to be more strongly associated with inclusion levels, and that this association seems to be mediated by proximity (linear or on tri-dimensional space) to promoter regions. The findings in Gonzalez-Vallines et al. (2015) suggest the possibility that our promoter-like exons have enhancer-like characteristicis.

On 2016 Mar 23, Eduardo Eyraa commented:

The authors failed to cite prior relevant literature related to the associations between chromatin signals and alternative splicing: Zhou Y, 2012, Shindo Y, 2013, Ye Z, 2014, Agirre E, 2015, González-Vallinas J, 2015, among others. Some of these articles already proposed specific predictive models of splicing regulation based on chromatin signals that can explain a considerable number of events. For instance, Agirre E, 2015 already showed that nearly 70% of differentially spliced events between two cell lines can be explained by a model based on the differential enrichment of chromatin signals. The proposed model included the binding activity of CTCF, which, incidentally, is also used in the model by Curado et al. On the other hand, Curado et al. describe their promoter-like exons in the following way: "...while no promoters themselves, they are, on average, closer to TSS and enriched by ChIA-PET tags associated with RNA Polymerase II". In one of the prior publications mentioned above, González-Vallinas J, 2015, the authors describe a model in which potential intragenic transcriptional enhancers, upon activation or deactivation, would change the local properties of the chromatin, thereby affecting the RNA processing of the host gene, and in particular, its alternative splicing. These potential intragenic enhancers are also shown to have enhancer-like properties, including the presence of ChIA-PET links with nearby promoters. Additionally, they produce eRNAs, they can occur on exons as well as on introns, and associate with differential splicing of nearby exons. It is unfortunate that the authors did not mention these prior results in their article, given the relevance they have for what they are discussing. If you are considering citing this publication, please consider whether you should also cite Agirre E, 2015 or González-Vallinas J, 2015.

On 2016 Mar 23, Eduardo Eyraa commented:

The authors failed to cite prior relevant literature related to the associations between chromatin signals and alternative splicing: Zhou Y, 2012, Shindo Y, 2013, Ye Z, 2014, Agirre E, 2015, González-Vallinas J, 2015, among others. Some of these articles already proposed specific predictive models of splicing regulation based on chromatin signals that can explain a considerable number of events. For instance, Agirre E, 2015 already showed that nearly 70% of differentially spliced events between two cell lines can be explained by a model based on the differential enrichment of chromatin signals. The proposed model included the binding activity of CTCF, which, incidentally, is also used in the model by Curado et al. On the other hand, Curado et al. describe their promoter-like exons in the following way: "...while no promoters themselves, they are, on average, closer to TSS and enriched by ChIA-PET tags associated with RNA Polymerase II". In one of the prior publications mentioned above, González-Vallinas J, 2015, the authors describe a model in which potential intragenic transcriptional enhancers, upon activation or deactivation, would change the local properties of the chromatin, thereby affecting the RNA processing of the host gene, and in particular, its alternative splicing. These potential intragenic enhancers are also shown to have enhancer-like properties, including the presence of ChIA-PET links with nearby promoters. Additionally, they produce eRNAs, they can occur on exons as well as on introns, and associate with differential splicing of nearby exons. It is unfortunate that the authors did not mention these prior results in their article, given the relevance they have for what they are discussing. If you are considering citing this publication, please consider whether you should also cite Agirre E, 2015 or González-Vallinas J, 2015.

On 2016 Apr 14, RODERIC GUIGO commented:

The literature cite by Eduard is relevant to the topic of the relationship between histone modifications and splicing. These works, as well as others, show that there is a weak (and sometimes controversial) effect of histone modifications and exon inclusion. This weak effect could reflect a general weak effect on most exons, or a stronger effect on a smaller set of exons. The main contribution of Curado et al. (2015) is the identification of a small set of exons in which histone modifications seem to be more strongly associated with inclusion levels, and that this association seems to be mediated by proximity (linear or on tri-dimensional space) to promoter regions. The findings in Gonzalez-Vallines et al. (2015) suggest the possibility that our promoter-like exons have enhancer-like characteristicis.