Hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) also known as cardiovascular helix-loop-helix factor 1 (CHF1) is a protein that in humans is encoded by the HEY2gene.
This protein is a type of transcription factor that belongs to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. It forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress transcription. During embryonic development, this mechanism is used to control the number of cells that develop into cardiac progenitor cells and myocardial cells.  The relationship is inversely related, so as the number of cells that express the Hey2 gene increases, the more CHF1 is present to repress transcription and the number of cells that take on a myocardial fate decreases. 
The expression of the Hey2 gene is induced by the Notch signaling pathway. In this mechanism, adjacent cells bind via transmembrane notch receptors. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternatively spliced transcript variants have been found, but their biological validity has not been determined.
The Hey2 gene is involved with the formation of the cardiovascular system and especially the heart itself.  Although studies have not been conducted about the effects of a malfunction in Hey2 expression in humans, experiments done with mice suggest this gene could be responsible for a number of heart defects. Using a gene knockout technique, scientists inactivated both the Hey1 and Hey2 genes of mice. The loss of these two genes resulted in death of the embryo 9.5 days after conception. It was found that the developing hearts of these embryos lacked most structural formations which resulted in massive hemorrhage. When only the Hey1 gene was knocked out, no apparent phenotypic changes occurred, suggesting that these two genes carry similar and redundant information for the development of the heart.
^Leimeister C, Externbrink A, Klamt B, Gessler M (July 1999). "Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis". Mechanisms of Development. 85 (1–2): 173–7. doi:10.1016/S0925-4773(99)00080-5. PMID10415358.
^ abcGibb N, Lazic S, Yuan X, Deshwar AR, Leslie M, Wilson MD, Scott IC (November 2018). "Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development". Development. 145 (22): dev167510. doi:10.1242/dev.167510. PMID30355727.
^Takata T, Ishikawa F (January 2003). "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression". Biochemical and Biophysical Research Communications. 301 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID12535671.
Iso T, Kedes L, Hamamori Y (March 2003). "HES and HERP families: multiple effectors of the Notch signaling pathway". Journal of Cellular Physiology. 194 (3): 237–55. doi:10.1002/jcp.10208. PMID12548545.
Kokubo H, Miyagawa-Tomita S, Johnson RL (July 2005). "Hesr, a mediator of the Notch signaling, functions in heart and vessel development". Trends in Cardiovascular Medicine. 15 (5): 190–4. doi:10.1016/j.tcm.2005.05.005. PMID16165016.
Chin MT, Maemura K, Fukumoto S, Jain MK, Layne MD, Watanabe M, Hsieh CM, Lee ME (March 2000). "Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system". The Journal of Biological Chemistry. 275 (9): 6381–7. doi:10.1074/jbc.275.9.6381. PMID10692439.
Steidl C, Leimeister C, Klamt B, Maier M, Nanda I, Dixon M, Clarke R, Schmid M, Gessler M (June 2000). "Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family". Genomics. 66 (2): 195–203. doi:10.1006/geno.2000.6200. PMID10860664.
Takata T, Ishikawa F (January 2003). "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression". Biochemical and Biophysical Research Communications. 301 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID12535671.
Fischer A, Klamt B, Schumacher N, Glaeser C, Hansmann I, Fenge H, Gessler M (September 2004). "Phenotypic variability in Hey2 -/- mice and absence of HEY2 mutations in patients with congenital heart defects or Alagille syndrome". Mammalian Genome. 15 (9): 711–6. doi:10.1007/s00335-004-2389-x. PMID15389319.
Kokubo H, Miyagawa-Tomita S, Nakazawa M, Saga Y, Johnson RL (February 2005). "Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system". Developmental Biology. 278 (2): 301–9. doi:10.1016/j.ydbio.2004.10.025. PMID15680351.
Doi H, Iso T, Yamazaki M, Akiyama H, Kanai H, Sato H, et al. (November 2005). "HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (11): 2328–34. doi:10.1161/01.ATV.0000185829.47163.32. PMID16151017.