On 2016 May 09, Attila Becskei commented:

Keung et al write that “An interesting result that emerged from our CR [chromatin regulator] library screens is that transcription can be repressed but not activated from downstream of a gene. Furthermore, activators do not appear to display the long-range properties that some repressors do”. This result confirms the conclusion of an earlier work (1). At the same time, Keung et al implicitly re-classified some repressors as activators (2).

(1) Basic mechanisms of transcription are conserved among eukaryotes; however, there are interesting quantitative differences. While genes can be activated from distant sites in higher eukaryotes, yeast genes can be controlled only from nearby sites in wild-type cells (Dobi KC, 2007). Only the Sir (silent information regulator) proteins have been known to display long-range (> 1kb) repression in yeast, which have a strong effect on chromatin structure(Nasmyth KA, 1982). Later, our study revealed that even classical repressors, such as Ssn6, can repress genes from distant sites provided they are positioned downstream of a gene (Ratna P, 2009,Kelemen JZ, 2010). An activator recruited to these downstream sites did not affect gene expression. In a set of synthetic gene reporters, three regulators (Ssn6, Sum1 and Sir3) had similar ranges of repression (Figure 3A in Becskei A, 2011). The range of repression from upstream (U) of a gene was considerably shorter than that from downstream (D) of the gene.

Using similar set of synthetic gene reporters, Keung et al recruited all known regulators to downstream sites. Interestingly, the our above conclusion was found to be true for all regulators: genes can be repressed but not activated from downstream sites.

(2) This uniform behavior of the repressors at the downstream sites is also interesting because a variable, non-uniform, behavior was observed by the authors at the upstream sites, i.e. at the promoter. For example, the classical yeast repressors, Ssn6, Tup1 and Ume6 did not repress expression when recruited to the promoter. Instead, they turned out to be the most potent activators of all regulators: they activated gene expression around 100 times (Figure 2B) (< PMID: 24995982>). Previous studies indicate that they are potent repressors both in wild-type and synthetic contexts (Keleher CA, 1992,Smith RL, 2000,Kadosh D, 1997).

On 2016 May 09, Attila Becskei commented:

Keung et al write that “An interesting result that emerged from our CR [chromatin regulator] library screens is that transcription can be repressed but not activated from downstream of a gene. Furthermore, activators do not appear to display the long-range properties that some repressors do”. This result confirms the conclusion of an earlier work (1). At the same time, Keung et al implicitly re-classified some repressors as activators (2).

(1) Basic mechanisms of transcription are conserved among eukaryotes; however, there are interesting quantitative differences. While genes can be activated from distant sites in higher eukaryotes, yeast genes can be controlled only from nearby sites in wild-type cells (Dobi KC, 2007). Only the Sir (silent information regulator) proteins have been known to display long-range (> 1kb) repression in yeast, which have a strong effect on chromatin structure(Nasmyth KA, 1982). Later, our study revealed that even classical repressors, such as Ssn6, can repress genes from distant sites provided they are positioned downstream of a gene (Ratna P, 2009,Kelemen JZ, 2010). An activator recruited to these downstream sites did not affect gene expression. In a set of synthetic gene reporters, three regulators (Ssn6, Sum1 and Sir3) had similar ranges of repression (Figure 3A in Becskei A, 2011). The range of repression from upstream (U) of a gene was considerably shorter than that from downstream (D) of the gene.

Using similar set of synthetic gene reporters, Keung et al recruited all known regulators to downstream sites. Interestingly, the our above conclusion was found to be true for all regulators: genes can be repressed but not activated from downstream sites.

(2) This uniform behavior of the repressors at the downstream sites is also interesting because a variable, non-uniform, behavior was observed by the authors at the upstream sites, i.e. at the promoter. For example, the classical yeast repressors, Ssn6, Tup1 and Ume6 did not repress expression when recruited to the promoter. Instead, they turned out to be the most potent activators of all regulators: they activated gene expression around 100 times (Figure 2B) (< PMID: 24995982>). Previous studies indicate that they are potent repressors both in wild-type and synthetic contexts (Keleher CA, 1992,Smith RL, 2000,Kadosh D, 1997).