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

Autor: Jyothi Thimmapuram, Avi Shamay, Aridany Suarez-Trujillo, Shelby Cummings, Clare Aduwari, Phillip San Miguel, Ketaki Bhide, Sameer J. Mabjeesh, Katelyn Huff, Kelsey Teeple, Theresa Casey, Jennifer Crodian, Karen Plaut
Rok vydání: 2021
Předmět:
Physiology
Cellular differentiation
Cell
Circadian clock
Biochemistry
Ion Channels
Mice
Cell Signaling
CRISPR-Associated Protein 9
Lactation
Membrane Receptor Signaling
Lipoprotein Receptors
Gene Editing
Multidisciplinary
Physics
ARNTL Transcription Factors
Cell Differentiation
Milk Proteins
Hormone Receptor Signaling
Cell biology
Electrophysiology
Circadian Rhythms
medicine.anatomical_structure
Gene Knockdown Techniques
Physical Sciences
Medicine
Female
Research Article
Signal Transduction
Transmembrane Receptors
SOD3
Science
Lipoproteins
Biophysics
Neurophysiology
Anemia
Sickle Cell

Biology
Mammary Glands
Animal

Cell surface receptor
medicine
Animals
Transcription factor
Gene
Prolactin receptor
Biology and Life Sciences
Proteins
Lipid metabolism
Epithelial Cells
Cell Biology
Ligand-Gated Ion Channels
Gene Expression Regulation
CRISPR-Cas Systems
Nuclear Receptor Signaling
Chronobiology
Neuroscience
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 8, p e0248199 (2021)
ISSN: 1932-6203
Popis: 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 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 (pSod3). Q-PCR 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.
Databáze: OpenAIRE