Intragenic transcriptional interference regulates the human immune ligand MICA

Many human genes have tandem promoters driving overlapping transcription, but the value of this distributed promoter configuration is generally unclear. Here we show that MICA, a gene encoding a ligand for the activating immune receptor NKG2D, contains a conserved upstream promoter that expresses a...

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Main Authors: Lin, D, Hiron, T, O'Callaghan, C
Format: Journal article
Published: EMBO Press 2018
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author Lin, D
Hiron, T
O'Callaghan, C
author_facet Lin, D
Hiron, T
O'Callaghan, C
author_sort Lin, D
collection OXFORD
description Many human genes have tandem promoters driving overlapping transcription, but the value of this distributed promoter configuration is generally unclear. Here we show that MICA, a gene encoding a ligand for the activating immune receptor NKG2D, contains a conserved upstream promoter that expresses a noncoding transcript. Transcription from the upstream promoter represses the downstream standard promoter activity in cis through transcriptional interference. The effect of transcriptional interference depends on the strength of transcription from the upstream promoter and can be described quantitatively by a simple reciprocal repressor function. Transcriptional interference coincides with recruitment at the standard downstream promoter of the FACT histone chaperone complex, which is involved in nucleosomal remodelling during transcription. The mechanism is invoked in the regulation of MICA expression by the physiological inputs interferon‐γ and interleukin‐4 that act on the upstream promoter. Genome‐wide analysis indicates that transcriptional interference between tandem intragenic promoters may constitute a general mechanism with widespread importance in human transcriptional regulation.
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spelling oxford-uuid:5c4c3e99-a786-4e30-9154-f04e2c056d0d2022-03-26T17:27:20ZIntragenic transcriptional interference regulates the human immune ligand MICAJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5c4c3e99-a786-4e30-9154-f04e2c056d0dSymplectic Elements at OxfordEMBO Press2018Lin, DHiron, TO'Callaghan, CMany human genes have tandem promoters driving overlapping transcription, but the value of this distributed promoter configuration is generally unclear. Here we show that MICA, a gene encoding a ligand for the activating immune receptor NKG2D, contains a conserved upstream promoter that expresses a noncoding transcript. Transcription from the upstream promoter represses the downstream standard promoter activity in cis through transcriptional interference. The effect of transcriptional interference depends on the strength of transcription from the upstream promoter and can be described quantitatively by a simple reciprocal repressor function. Transcriptional interference coincides with recruitment at the standard downstream promoter of the FACT histone chaperone complex, which is involved in nucleosomal remodelling during transcription. The mechanism is invoked in the regulation of MICA expression by the physiological inputs interferon‐γ and interleukin‐4 that act on the upstream promoter. Genome‐wide analysis indicates that transcriptional interference between tandem intragenic promoters may constitute a general mechanism with widespread importance in human transcriptional regulation.
spellingShingle Lin, D
Hiron, T
O'Callaghan, C
Intragenic transcriptional interference regulates the human immune ligand MICA
title Intragenic transcriptional interference regulates the human immune ligand MICA
title_full Intragenic transcriptional interference regulates the human immune ligand MICA
title_fullStr Intragenic transcriptional interference regulates the human immune ligand MICA
title_full_unstemmed Intragenic transcriptional interference regulates the human immune ligand MICA
title_short Intragenic transcriptional interference regulates the human immune ligand MICA
title_sort intragenic transcriptional interference regulates the human immune ligand mica
work_keys_str_mv AT lind intragenictranscriptionalinterferenceregulatesthehumanimmuneligandmica
AT hiront intragenictranscriptionalinterferenceregulatesthehumanimmuneligandmica
AT ocallaghanc intragenictranscriptionalinterferenceregulatesthehumanimmuneligandmica