Chromosomal contact permits transcription between coregulated genes.
Transcription of coregulated genes occurs in the context of long-range chromosomal contacts that form multigene complexes. Such contacts and transcription are lost in knockout studies of transcription factors and structural chromatin proteins. To ask whether chromosomal contacts are required for cotranscription in multigene complexes, we devised a strategy using TALENs to cleave and disrupt gene loops in a well-characterized multigene complex. Monitoring this disruption using RNA FISH and immunofluorescence microscopy revealed that perturbing the site of contact had a direct effect on transcription of other interacting genes. Unexpectedly, this effect on cotranscription was hierarchical, with dominant and subordinate members of the multigene complex engaged in both intra- and interchromosomal contact. This observation reveals the profound influence of these chromosomal contacts on the transcription of coregulated genes in a multigene complex.
Gene Expression and Biophysics Group, Synthetic Biology Emerging Research Area, Biosciences Unit, Council for Scientific and Industrial Research, Pretoria, Gauteng 0001, South Africa.
Stephanie
S
Fanucchi
Youtaro
Y
Shibayama
Shaun
S
Burd
Marc S
MS
Weinberg
Musa M
MM
Mhlanga
D002875:Chromosomes / Q000737:chemistry; D003851:Deoxyribonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D005821:Genetic Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012097:Repressor Proteins / Q000235:genetics; D059010:Single-Cell Analysis; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012097:Repressor Proteins; C507993:SAMD4A protein, human; D014409:Tumor Necrosis Factor-alpha; D003851:Deoxyribonucleases