The BEAF-32 insulator coordinates genome organization and function during the evolution of Drosophila species

Abstract

Understanding the relationship between genome organization and expression is central to understanding genome function. Closely apposed genes in a head-to-head orientation share the same upstream region and are likely to be coregulated. Here we identify the Drosophila BEAF-32 insulator as a cis regulatory element separating close head-to-head genes with different transcription regulation modes. We then compare the binding landscapes of the BEAF-32 insulator protein in four different Drosophila genomes and highlight the evolutionarily conserved presence of this protein between close adjacent genes. We find that changes in binding of BEAF-32 to sites in the genome of different Drosophila species correlate with alterations in genome organization caused by DNA rearrangements or genome size expansion. The cross-talk between BEAF-32 genomic distribution and genome organization contributes to new gene-expression profiles, which in turn translate into specific and distinct phenotypes. The results suggest a mechanism for the establishment of differences in transcription patterns during evolution.

Two new insulator proteins, Pita and ZIPIC, target CP190 to chromatin

“…This has been shown for CP190 (Bartkuhn et al 2009), for dCTCF (N egre et al 2010, and for BEAF-32 (Bushey et al 2009;Jiang et al 2009;N egre et al 2010;Yang et al 2012). Similarly, we find a strong correlation between Pita and ZIPIC binding to transcriptional start sites and gene activity.…”

“…Taking into account data on the association of BEAF-32 and CP190 with actively transcribed genes (Bartkuhn et al 2009;Jiang et al 2009;Yang et al 2012), we were interested in finding out whether there is a correlation between transcription levels and Pita or ZIPIC binding. Therefore, we calculated the maximum coverage within an interval of -1 to +1 kb around the transcription start site for each transcription unit and sorted the units accordingly into four equal-sized groups.…”

Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle

“…However, BEAF-32 displays a similar distribution pattern, but has been recently shown to act as an insulator to allow independent regulation of close adjacent divergently transcribed genes. 39 sequences instead. The presence of DREF at genomic sites lacking its consensus sequence but containing binding motifs for Su(Hw) or dCTCF may suggest that DREF does not directly bind to these sites and is, instead, recruited through direct or indirect interactions with other insulator proteins.…”

“…[36][37][38] For example, BEAF-32 is found more often close to gene promoters, where it appears to confer independent regulation to closely adjacent, divergently transcribed genes. 39 On the other hand, Su(Hw) tends to be present in intergenic regions next to genes transcribed at low levels. 36 In addition, insulators appear to play overlapping roles at some genomic locations, where several different insulator DNA-binding proteins cluster together.…”

The BEAF-32 insulator protein is required for Hippo pathway activity in the terminal differentiation of neuronal subtypes

“…BEAF binds preferentially near promoters at several thousand sites in the genome (Emberly et al, 2008;Jiang et al, 2009;Negre et al, 2011;Yang et al, 2012) and generally promotes gene expression. Two BEAF isoforms, BEAF-32A and BEAF-32B, are identical except for the 80 amino acid DNA-binding domain; however, BEAF-32B appears to be the dominant isoform (Jiang et al, 2009;Roy et al, 2007).…”