Transcriptional interference by small transcripts in proximal promoter regions

Area of Science:

• Genomics
• Molecular Biology
• Gene Regulation

Background:

• Proximal promoter regions (PPR) are transcribed into small RNAs.
• Transcription within PPRs may regulate downstream genes via transcriptional interference (TI).

Purpose of the Study:

• Investigate small RNA transcripts in human RefSeq gene PPRs.
• Analyze the role of these transcripts in regulating gene expression through TI.

Main Methods:

• Analyzed capped and polyadenylated small RNAs in human RefSeq gene PPRs across eight cell lines.
• Intersected small RNA transcript data with transcription factor binding sites (TFBS).
• Correlated small RNA expression with TF DNA binding affinities and chromatin landscapes (ChIA-PET).

Main Results:

• Small RNA transcripts overlapping TFBS showed a negative correlation between expression and TF DNA binding affinity, indicating TI.
• These TF-binding interfering transcripts (TFbiTrs) were cell-line specific.
• Higher TF/DNA binding affinities and gene expression were observed in the absence of TFbiTrs.
• Distal enhancers were involved in TFbiTr transcription, acting as repressors for downstream genes.

Conclusions:

• Transcriptional interference by TFbiTrs significantly impacts gene expression.
• Enhancers can regulate TFbiTrs, thereby controlling downstream gene expression.
• TI is a crucial mechanism in gene expression regulation.