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Transcriptional regulation of CYP19 by cohesin-mediated chromosome tethering in human granulosa cells.

ABSTRACT: Human CYP19 spans a region of chromosome 15 of approximately 130 kb and encodes aromatase, an enzyme required for estrogen synthesis. In the human granulosa cell-line KGN, there are seven open chromatin regions within the CYP19 locus. In this study, we demonstrate that two of these regions ~40 kb upstream and ~15 kb downstream of the CYP19 promoter are cohesin-loading sites, physically interacting with the promoter to negatively and positively regulate transcription, respectively. These observations suggest that CYP19 expression is controlled by a balance between the upstream silencer and downstream enhancer. When cohesin is depleted, CYP19 expression is elevated since the silencer is 2.5-fold further from the promoter than the enhancer and most likely depends on cohesin-mediated tethering to influence expression.

SUBMITTER: Kotomura N

PROVIDER: S-EPMC8326343 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Transcriptional regulation of CYP19 by cohesin-mediated chromosome tethering in human granulosa cells.

Kotomura Naoe N Harada Nobuhiro N Shimono Yohei Y Ishihara Satoru S

Biochemistry and biophysics reports 20210724

Human CYP19 spans a region of chromosome 15 of approximately 130 kb and encodes aromatase, an enzyme required for estrogen synthesis. In the human granulosa cell-line KGN, there are seven open chromatin regions within the CYP19 locus. In this study, we demonstrate that two of these regions ~40 kb upstream and ~15 kb downstream of the CYP19 promoter are cohesin-loading sites, physically interacting with the promoter to negatively and positively regulate transcription, respect ...[more]

PMID: 34368471

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