Regulatory architecture of housekeeping genes is driven by promoter assemblies
Marion Dejosez,
Alessandra Dall’Agnese,
Mahesh Ramamoorthy,
Jesse Platt,
Xing Yin,
Megan Hogan,
Ran Brosh,
Abraham S. Weintraub,
Denes Hnisz,
Brian J. Abraham,
Richard A. Young,
Thomas P. Zwaka
Affiliations
Marion Dejosez
Black Family Stem Cell Institute, Huffington Center for Cell-based Research in Parkinson’s Disease, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA
Alessandra Dall’Agnese
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
Mahesh Ramamoorthy
Black Family Stem Cell Institute, Huffington Center for Cell-based Research in Parkinson’s Disease, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA
Jesse Platt
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
Xing Yin
Black Family Stem Cell Institute, Huffington Center for Cell-based Research in Parkinson’s Disease, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA
Megan Hogan
Black Family Stem Cell Institute, Huffington Center for Cell-based Research in Parkinson’s Disease, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA
Ran Brosh
Black Family Stem Cell Institute, Huffington Center for Cell-based Research in Parkinson’s Disease, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA
Abraham S. Weintraub
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
Denes Hnisz
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Brian J. Abraham
St. Jude Research Children’s Hospital, Memphis, TN 38105, USA
Richard A. Young
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Corresponding author
Thomas P. Zwaka
Black Family Stem Cell Institute, Huffington Center for Cell-based Research in Parkinson’s Disease, Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Corresponding author
Summary: Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping functions, whose regulation is essential for normal cell metabolism and growth, generally lack interactions with distal enhancers. We find that Ronin (Thap11) assembles multiple promoters of housekeeping and metabolic genes to regulate gene expression. This behavior is analogous to how enhancers are brought together with promoters to regulate cell identity genes. Thus, Ronin-dependent promoter assemblies provide a mechanism to explain why housekeeping genes can forgo distal enhancer elements and why Ronin is important for cellular metabolism and growth control. We propose that clustering of regulatory elements is a mechanism common to cell identity and housekeeping genes but is accomplished by different factors binding distinct control elements to establish enhancer-promoter or promoter-promoter interactions, respectively.
