Abstract
BackgroundDrosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that expressed from the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space largely independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome.ResultsHere, we demonstrate that CLAMP promotes the observed three-dimensional clustering of MSLc binding sites. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range three-dimensional interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes three-dimensional interactions between active chromatin regions together with other insulator proteins.ConclusionOverall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.
Highlights
Three-dimensional chromatin domains are important for coordinating gene regulation
We demonstrate that chromatin-linked adapter for MSL proteins (CLAMP) primarily promotes long-range interactions within active chromatin regions, including chromatin entry” sites (CES)
CLAMP promotes long‐range three‐dimension interactions on the X‐chromosome more strongly than on autosomes In order to understand how CLAMP regulates the threedimensional organization of the genome, we performed in situ chromosome conformation capture with highthroughput sequencing [36] using HindIII, a 6-bp cutter restriction enzyme, in Drosophila male Schneider’s line 2 (S2) [37] cultured cells after validated RNAi depletion of either gfp or clamp [4, 19, 20]
Summary
Three-dimensional chromatin domains are important for coordinating gene regulation. Dosage compensation in Drosophila provides one of the few model systems for studying the formation of a large hyper-active chromatin domain: approximately one thousand active genes along the length of the single male X-chromosome are coordinately upregulated twofold [4,5,6]. In Drosophila, the male-specific lethal complex (MSLc) forms only in males and is responsible for increasing transcript levels of X-linked genes along the length of the single male X-chromosome 1.4 fold, helping to equalize gene expression with that of females [4,5,6]. The male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that expressed from the two female X-chromosomes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
