Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.

The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epi...

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Autores principales:	Theresa Casey, Aridany Suarez-Trujillo, Shelby Cummings, Katelyn Huff, Jennifer Crodian, Ketaki Bhide, Clare Aduwari, Kelsey Teeple, Avi Shamay, Sameer J Mabjeesh, Phillip San Miguel, Jyothi Thimmapuram, Karen Plaut
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a08fea25c39a45f08ea4061d2b3ab467
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spelling	oai:doaj.org-article:a08fea25c39a45f08ea4061d2b3ab4672021-12-02T20:14:57ZCore circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.1932-620310.1371/journal.pone.0248199https://doaj.org/article/a08fea25c39a45f08ea4061d2b3ab4672021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0248199https://doaj.org/toc/1932-6203The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). RT-qPCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr), Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.Theresa CaseyAridany Suarez-TrujilloShelby CummingsKatelyn HuffJennifer CrodianKetaki BhideClare AduwariKelsey TeepleAvi ShamaySameer J MabjeeshPhillip San MiguelJyothi ThimmapuramKaren PlautPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0248199 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Theresa Casey Aridany Suarez-Trujillo Shelby Cummings Katelyn Huff Jennifer Crodian Ketaki Bhide Clare Aduwari Kelsey Teeple Avi Shamay Sameer J Mabjeesh Phillip San Miguel Jyothi Thimmapuram Karen Plaut Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
description	The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). RT-qPCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr), Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.
format	article
author	Theresa Casey Aridany Suarez-Trujillo Shelby Cummings Katelyn Huff Jennifer Crodian Ketaki Bhide Clare Aduwari Kelsey Teeple Avi Shamay Sameer J Mabjeesh Phillip San Miguel Jyothi Thimmapuram Karen Plaut
author_facet	Theresa Casey Aridany Suarez-Trujillo Shelby Cummings Katelyn Huff Jennifer Crodian Ketaki Bhide Clare Aduwari Kelsey Teeple Avi Shamay Sameer J Mabjeesh Phillip San Miguel Jyothi Thimmapuram Karen Plaut
author_sort	Theresa Casey
title	Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
title_short	Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
title_full	Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
title_fullStr	Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
title_full_unstemmed	Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
title_sort	core circadian clock transcription factor bmal1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a08fea25c39a45f08ea4061d2b3ab467
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Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.

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